Perceptions of risk of coronary heart disease among people living with type 2 diabetes mellitus.

PubMed

Ammouri, Ali Ahmad; Abu Raddaha, Ahmad H; Natarajan, Jansi; D'Souza, Melba Sheila

2018-02-01

Our aim is to assess perception of risk of developing coronary heart disease and to examine its associations with individuals' characteristics and health behaviours among Omani people with type 2 diabetes mellitus (T2DM). Evaluating perceptions of being at risk of developing a disease may give insight into health promotion behaviours. People with diabetes are at high risk of coronary heart disease. The management of diabetes mellitus should include prevention and control of coronary heart disease. A cross-sectional correlational study was conducted. A convenience sample of 160 adults with T2DM was invited to participate in this study between November 2014 and March 2015. Descriptive and regression analyses were performed to examine associations between study variables. Perception of risk of developing coronary heart disease was significantly associated with low educational level (β = 0.191, P < .05), low income (β = 0.201, P < .05), and high level of knowledge about diabetes mellitus (β = 0.200, P < .05). People with T2DM who perceived coronary heart disease as having few moderate known outcomes and consequences reported consuming healthy diet more frequently. Teaching people with T2DM about the risk of developing coronary heart disease is essential as it could motivate them to perform health promotion behaviours, which may assist in controlling and reducing coronary heart disease. © 2017 John Wiley & Sons Australia, Ltd.

Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio (Devario aequipinnatus) and Zebrafish (Danio rerio) Hearts

PubMed Central

Manalo, Trina; May, Adam; Quinn, Joshua; Lafontant, Dominique S.; Shifatu, Olubusola; He, Wei; Gonzalez-Rosa, Juan M.; Burns, Geoffrey C.; Burns, Caroline E.; Burns, Alan R.; Lafontant, Pascal J.

2016-01-01

Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish (Danio rerio) and giant danio (Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins—wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)—in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins’ ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID:27680670

Role of Myofibril-Inducing RNA in cardiac TnT expression in developing Mexican axolotl

PubMed Central

Sferrazza, Gian-Franco; Zhang, Chi; Jia, Pingping; Lemanski, Sharon L.; Athauda, Gagani; Stassi, Alyssa; Halager, Kristine; Maier, Jennifer A.; Rueda-de-Leon, Elena; Gupta, Amit; Dube, Syamalima; Huang, Xupei; Prentice, Howard M.; Dube, Dipak K.; Lemanski, Larry F.

2007-01-01

The Mexican axolotl, Ambystoma mexicanum, has been a useful animal model to study heart development and cardiac myofibrillogenesis. A naturally-occurring recessive mutant, gene “c”, for cardiac non-function in the Mexican axolotl causes a failure of myofibrillogenesis due to a lack of tropomyosin expression in homozygous mutant (c/c) embryonic hearts.. Myofibril-Inducing RNA (MIR) rescues mutant hearts in vitro by promoting tropomyosin expression and myofibril formation thereafter. We have studied the effect of MIR on the expression of various isoforms of cardiac Troponin-T (cTnT), a component of the thin filament that binds with tropomyosin. Four alternatively spliced cTnT isoforms have been characterized from developing axolotl heart. The expression of various cTnT isoforms in normal, mutant, and mutant hearts corrected with MIR, is evaluated by real-time RT-PCR using isoform specific primer pairs; MIR affects the total transcription as well as the splicing of the cTnT in axolotl heart PMID:17408593

Comparative study of myocardial high energy phosphate substrate content in slow and fast growing chicken and in chickens with heart failure and ascites.

PubMed

Olkowski, A A; Nain, S; Wojnarowicz, C; Laarveld, B; Alcorn, J; Ling, B B

2007-09-01

In order to explain the biochemical mechanisms associated with deteriorating heart function in broiler chickens, this study compared myocardial high energy phosphate substrates in leghorns, feed restricted (Broilers-Res) broilers, ad libitum fed broilers (Broilers-AL), and in broilers that developed heart failure and ascites. The profile of adenine nucleotide content in the heart tissue did not differ between leghorns and Broilers-Res, but there were significant differences among Broilers-Res, Broilers-AL, and broilers with ascites. During intensive growth periods, leghorns and Broilers-Res showed increasing trends in heart ATP levels, whereas in fast growing broilers the heart ATP declined (p<0.021). ATP:ADP and ATP:CrP ratios increased with age in both leghorn and Broilers-Res, declined in fast growing broilers, and were the lowest in broilers that developed heart failure. The changes in heart high energy phosphate profile in broilers suggest that the energy demand of the heart during a rapid growth phase may exceed the bird's metabolic capacity to supply adequate levels of high energy phosphate substrate. The insufficiency of energy substrate likely contributes to the declining heart rate. In some individuals this may lead to impaired heart pump function, and in more severe cases may progress to heart pump failure.

Between invisible defects and visible impact: the life experiences of adolescents and young adults with congenital heart disease.

PubMed

Chiang, Yueh-Tao; Chen, Chi-Wen; Su, Wen-Jen; Wang, Jou-Kou; Lu, Chun-Wei; Li, Yuh-Fen; Moons, Philip

2015-03-01

To describe the life experiences of adolescents and young adults with congenital heart disease. Owing to medical advances, most children with congenital heart disease are expected to survive into adulthood. The transitional development from adolescence to adult is the critical period for fostering self-care. Descriptive phenomenological study. Thirty-five patients of 15-24 years old with congenital heart disease were recruited from paediatric cardiology clinics by purposive sampling. They were individually interviewed between October 2012-February 2013 using a semi-structured interview guideline and joined adult congenital heart disease clinics at two medical centres in northern Taiwan. The data were analysed using descriptive phenomenological method developed by Giorgi. The essence of the life experience of adolescents and young adults with congenital heart disease involves a dynamic process of moving between invisible defects and coexistence with the disease. Six themes emerged: (1) invisible defects: the existence of imperfect understanding; (2) conflict: interpersonal frustrations; (3) imbalance: the loss of self-balance; (4) suffering: increasing anxiety; (5) encounters: meeting needs; and (6) coexistence: positive coping strategies. As patients with congenital heart disease transition from adolescence into adulthood, they must learn about their disease, overcome frustration and anxiety and develop self-care strategies for coexisting with congenital heart disease. Results of this study may serve as clinical care guidelines for adolescents and young adults with congenital heart disease and give a reference for developing transitional intervention strategies. © 2014 John Wiley & Sons Ltd.

Probing the Electrophysiology of the Developing Heart

PubMed Central

Watanabe, Michiko; Rollins, Andrew M.; Polo-Parada, Luis; Ma, Pei; Gu, Shi; Jenkins, Michael W.

2016-01-01

Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the creation and deployment of novel technologies along with the use of classical techniques on a range of animal models. Each tool has its strengths and limitations and has contributed to making key discoveries to expand our understanding of cardiac development. Further progress in understanding the mechanisms that regulate the normal and abnormal development of the electrophysiology of the heart requires integration of this functional information with the more extensively elucidated structural and molecular changes. PMID:29367561

A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy

PubMed Central

Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao

2015-01-01

Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential role in heart morphogenesis and function. PMID:26348211

Molecular and immunohistochemical analyses of cardiac troponin T during cardiac development in the Mexican axolotl, Ambystoma mexicanum.

PubMed

Zhang, C; Pietras, K M; Sferrazza, G F; Jia, P; Athauda, G; Rueda-de-Leon, E; Rveda-de-Leon, E; Maier, J A; Dube, D K; Lemanski, S L; Lemanski, L F

2007-01-01

The Mexican axolotl, Ambystoma mexicanum, is an excellent animal model for studying heart development because it carries a naturally occurring recessive genetic mutation, designated gene c, for cardiac nonfunction. The double recessive mutants (c/c) fail to form organized myofibrils in the cardiac myoblasts resulting in hearts that fail to beat. Tropomyosin expression patterns have been studied in detail and show dramatically decreased expression in the hearts of homozygous mutant embryos. Because of the direct interaction between tropomyosin and troponin T (TnT), and the crucial functions of TnT in the regulation of striated muscle contraction, we have expanded our studies on this animal model to characterize the expression of the TnT gene in cardiac muscle throughout normal axolotl development as well as in mutant axolotls. In addition, we have succeeded in cloning the full-length cardiac troponin T (cTnT) cDNA from axolotl hearts. Confocal microscopy has shown a substantial, but reduced, expression of TnT protein in the mutant hearts when compared to normal during embryonic development. 2006 Wiley-Liss, Inc.

[Use of antihypertensive drug therapy and risk of development of congestive heart failure].

PubMed

Sobrino, Javier; Plana, Jaume; Felip, Angela; Doménech, Mónica; Reth, Peter; Adrián, María Jesús; de la Sierra, Alejandro

2004-09-18

It has been suggested that the use of some antihypertensive agents may favour the development of congestive heart failure. The aim of the present study was to evaluate such a possible association in patients who had a new diagnosis of congestive heart failure. This was a retrospective case-control study of 81 patients who had a first hospital admission with a new diagnosis of congestive heart failure (cases) and 162 patients admitted for other hypertensive complications (controls). Previous antihypertensive drug use was registered and the possible association with congestive heart failure was evaluated. The presence of congestive heart failure was not associated with the use of any antihypertensive drug class. When treatments were grouped in classic (diuretics and betablockers) or modern (calcium channel blockers, angiotensin-converting-enzyme inhibitors, alphablockers or angiotensin receptor blockers), a negative association was observed with the latter group, which was observed in 48.1% of cases and 63.6% of controls (odds ratio: 0.532; 95% confidence interval, 0.310-0.913). This association was lost after adjustment for other cardiovascular risk factors or previous hypertensive complications. The development of congestive heart failure was not associated with the use of any specific antihypertensive drug class. From the present evidence, it is not possible to recommend a specific antihypertensive agent in patients at risk of developing congestive heart failure but without evidence of such disease.

2013 update on congenital heart disease, clinical cardiology, heart failure, and heart transplant.

PubMed

Subirana, M Teresa; Barón-Esquivias, Gonzalo; Manito, Nicolás; Oliver, José M; Ripoll, Tomás; Lambert, Jose Luis; Zunzunegui, José L; Bover, Ramon; García-Pinilla, José Manuel

2014-03-01

This article presents the most relevant developments in 2013 in 3 key areas of cardiology: congenital heart disease, clinical cardiology, and heart failure and transplant. Within the area of congenital heart disease, we reviewed contributions related to sudden death in adult congenital heart disease, the importance of specific echocardiographic parameters in assessing the systemic right ventricle, problems in patients with repaired tetralogy of Fallot and indication for pulmonary valve replacement, and confirmation of the role of specific factors in the selection of candidates for Fontan surgery. The most recent publications in clinical cardiology include a study by a European working group on correct diagnostic work-up in cardiomyopathies, studies on the cost-effectiveness of percutaneous aortic valve implantation, a consensus document on the management of type B aortic dissection, and guidelines on aortic valve and ascending aortic disease. The most noteworthy developments in heart failure and transplantation include new American guidelines on heart failure, therapeutic advances in acute heart failure (serelaxin), the management of comorbidities such as iron deficiency, risk assessment using new biomarkers, and advances in ventricular assist devices. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

The integration of an online module on student learning.

PubMed

Yehle, Karen S; Chang, Karen

2012-11-01

Heart failure is a prevalent and costly condition. Patients with better self-management are less likely to be rehospitalized. An online interactive heart failure module was developed and integrated into a medical-surgical nursing course to assist students in learning how to care for patients with heart failure. The purpose of this study was to examine whether the integration of an online heart failure module improved baccalaureate nursing students' heart failure self-management knowledge. A pretest/posttest design was used to examine the effects of student knowledge of heart failure self-management following implementation of an online module. Among 235 students, significant improvement of heart failure self-management knowledge was observed (P < .05). The mean posttest scores ranged from 13.82 to 15.93. Students had problems mastering knowledge of weight monitoring, use of nonsteroidal anti-inflammatory drugs, symptoms to report to physicians, and potassium-based salt substitutes. These findings were similar to four studies examining nurses' knowledge of heart failure. Students and nurses have difficulty mastering similar heart failure education concepts. An additional strategy, such as simulated or case scenarios, needs to be developed to help nurses and nursing students master all key concepts of heart failure self-management.

Clinical trials update: highlights of the scientific sessions of the American Heart Association year 2000: Val HeFT, COPERNICUS, MERIT, CIBIS-II, BEST, AMIOVIRT, V-MAC, BREATHE, HEAT, MIRACL, FLORIDA, VIVA and the first human cardiac skeletal muscle myoblast transfer for heart failure.

PubMed

Thackray, S D; Witte, K K; Khand, A; Dunn, A; Clark, A L; Cleland, J G

2001-01-01

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at scientific sessions of the American Heart Association in November 2000. Clinical studies of particular interest to people caring for patients with heart failure include Val-HeFT, AMIOVIRT and V-MAC. New data from beta-blockers trials are reviewed, highlights from some important developments in post-infarction care, including MIRACL and FLORIDA, discussed and results of some early studies of gene therapy reported.

The effects of incubation temperature and experimental design on heart rates of lizard embryos.

PubMed

Hulbert, Austin C; Mitchell, Timothy S; Hall, Joshua M; Guiffre, Cassia M; Douglas, Danielle C; Warner, Daniel A

2017-08-01

Many studies of phenotypic plasticity alter environmental conditions during embryonic development, yet only measure phenotypes at the neonatal stage (after embryonic development). However, measuring aspects of embryo physiology enhances our understanding of how environmental factors immediately affect embryos, which aids our understanding of developmental plasticity. While current research on reptile developmental plasticity has demonstrated that fluctuating incubation temperatures affect development differently than constant temperatures, most research on embryo physiology is still performed with constant temperature experiments. In this study, we noninvasively measured embryonic heart rates of the brown anole (Anolis sagrei), across ecologically relevant fluctuating temperatures. We incubated eggs under temperatures measured from potential nests in the field and examined how heart rates change through a diel cycle and throughout embryonic development. We also evaluated how experimental design (e.g., repeated vs. single measures designs, constant vs. fluctuating temperatures) and different protocols (e.g., removing eggs from incubators) might influence heart rate. We found that heart rates were correlated with daily temperature and increased through development. Our findings suggest that experimenters have reasonable flexibility in choosing an experimental design to address their questions; however, some aspects of design and protocol can potentially influence estimations of heart rates. Overall, we present the first ecologically relevant measures of anole embryonic heart rates and provide recommendations for experimental designs for future experiments. © 2017 Wiley Periodicals, Inc.

The Failing Heart Relies on Ketone Bodies as a Fuel.

PubMed

Aubert, Gregory; Martin, Ola J; Horton, Julie L; Lai, Ling; Vega, Rick B; Leone, Teresa C; Koves, Timothy; Gardell, Stephen J; Krüger, Marcus; Hoppel, Charles L; Lewandowski, E Douglas; Crawford, Peter A; Muoio, Deborah M; Kelly, Daniel P

2016-02-23

Significant evidence indicates that the failing heart is energy starved. During the development of heart failure, the capacity of the heart to utilize fatty acids, the chief fuel, is diminished. Identification of alternate pathways for myocardial fuel oxidation could unveil novel strategies to treat heart failure. Quantitative mitochondrial proteomics was used to identify energy metabolic derangements that occur during the development of cardiac hypertrophy and heart failure in well-defined mouse models. As expected, the amounts of proteins involved in fatty acid utilization were downregulated in myocardial samples from the failing heart. Conversely, expression of β-hydroxybutyrate dehydrogenase 1, a key enzyme in the ketone oxidation pathway, was increased in the heart failure samples. Studies of relative oxidation in an isolated heart preparation using ex vivo nuclear magnetic resonance combined with targeted quantitative myocardial metabolomic profiling using mass spectrometry revealed that the hypertrophied and failing heart shifts to oxidizing ketone bodies as a fuel source in the context of reduced capacity to oxidize fatty acids. Distinct myocardial metabolomic signatures of ketone oxidation were identified. These results indicate that the hypertrophied and failing heart shifts to ketone bodies as a significant fuel source for oxidative ATP production. Specific metabolite biosignatures of in vivo cardiac ketone utilization were identified. Future studies aimed at determining whether this fuel shift is adaptive or maladaptive could unveil new therapeutic strategies for heart failure. © 2016 American Heart Association, Inc.

Women's perceptions of heart disease and breast cancer and the association with media representations of the diseases

PubMed Central

Berry, Tanya R.; Stearns, Jodie A.; Courneya, Kerry S.; McGannon, Kerry R.; Norris, Colleen M.; Rodgers, Wendy M.; Spence, John C.

2016-01-01

Abstract Background This research examined differences in perceptions of heart disease compared with breast cancer and if the differences are reflected in media presentations of the diseases. Relationships of differences in perceptions to demographic groups, heart disease risk factors and health behaviors were examined. Methods Study 1 was a quantitative content analysis of articles and advertisements related to heart disease or breast cancer. Results There were greater perceptions of susceptibility, preventability and controllability of heart disease and lower perceptions regarding seriousness, fearfulness and extent to which family history determines disease development of heart disease compared with breast cancer. Five times more pieces related to breast cancer were found compared with heart disease. Study 2 was a survey of 1524 women. More articles and advertisements about breast cancer than heart disease were found, and survey participants reported seeing significantly more breast cancer than heart disease media. Younger women had greater perceived susceptibility of breast cancer relative to heart disease while the content analysis revealed that the heart disease pieces were more likely to feature women older than 40 years of age. Conclusions This research is an important step in the development of theories regarding causal effects of media on health perceptions and behaviors. PMID:28158680

[Surgery of grown up congenital heart disease. About 540 cases].

PubMed

Haddad, A; Bourezak, R; Aouiche, M; Ait Mohand, R; Hamzaoui, A; Bourezak, S E

2015-09-01

With advances in recent decades in the field of congenital heart disease both for imaging in medical therapy, a large number of heart disease is diagnosed before birth. Many of them benefit from surgery and reach adulthood, they do not require further action. Some of them develop later in their lives other problems requiring reoperation in adulthood. This sparked the birth of a subspecialty within the department of congenital heart disease: GUCH Unit "grown up congenital heart disease". In developing countries, little heart are detected in childhood, a minority of them are operated and very few reach adulthood or with minor heart disease or become advanced enough then inoperable. Only part may still take advantage of surgery at this age. The aim of our study is to describe the spectrum and characteristics of congenital heart disease in adulthood in Algiers a center of cardiovascular surgery. A retrospective descriptive study of patients aged 15 and above operated for congenital heart defects between 1995 and 2011. Five hundred and forty patients aged 15 to 76years (29±10 years), including 314 women and 226 men are operated congenital heart defects between 1995 and 2011. The left-right shunts represent two thirds of heart disease, represented mainly (50%) by the atrial septal defect. Barriers to the ejection of the left heart represent one forth of cases with a predominance of subvalvular aortic stenosis. We find the native heart whose survival is considered exceptional in adulthood in the absence of surgery, such as tetralogy of Fallot, aortopulmonary windows wide, double outlet right ventricle and atrioventricular canal that take advantage of always surgery. The results are encouraging with low perioperative mortality (2%). The approach of congenital heart disease in developing countries is different from that of developed countries. Efforts need to be made in early detection and monitoring of congenital heart disease and improve access to surgery centers in close collaboration with pediatricians, cardiologists and obstetricians. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies.

PubMed

Tzatzalos, Evangeline; Abilez, Oscar J; Shukla, Praveen; Wu, Joseph C

2016-01-15

Engineered heart tissue has emerged as a personalized platform for drug screening. With the advent of induced pluripotent stem cell (iPSC) technology, patient-specific stem cells can be developed and expanded into an indefinite source of cells. Subsequent developments in cardiovascular biology have led to efficient differentiation of cardiomyocytes, the force-producing cells of the heart. iPSC-derived cardiomyocytes (iPSC-CMs) have provided potentially limitless quantities of well-characterized, healthy, and disease-specific CMs, which in turn has enabled and driven the generation and scale-up of human physiological and disease-relevant engineered heart tissues. The combined technologies of engineered heart tissue and iPSC-CMs are being used to study diseases and to test drugs, and in the process, have advanced the field of cardiovascular tissue engineering into the field of precision medicine. In this review, we will discuss current developments in engineered heart tissue, including iPSC-CMs as a novel cell source. We examine new research directions that have improved the function of engineered heart tissue by using mechanical or electrical conditioning or the incorporation of non-cardiomyocyte stromal cells. Finally, we discuss how engineered heart tissue can evolve into a powerful tool for therapeutic drug testing. Copyright © 2015 Elsevier B.V. All rights reserved.

Topography of aortic heart valves. [applied to the development of a prosthetic heart valve

NASA Technical Reports Server (NTRS)

Karara, H. M.

1974-01-01

The cooperative effort towards the development of a tri-leaflet prosthetic heart valve is described. The photogrammetric studies were conducted on silicone rubber molds. Information on data acquisition and data reduction phases is given, and certain accuracy aspects of the project are explained. The various outputs which are discussed include digital models, profiles, and contour maps.

A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying Vertebrate Cardiogenesis and Congenital Heart Defects

PubMed Central

Hempel, Annemarie; Kühl, Michael

2016-01-01

The African clawed frog, Xenopus, is a valuable non-mammalian model organism to investigate vertebrate heart development and to explore the underlying molecular mechanisms of human congenital heart defects (CHDs). In this review, we outline the similarities between Xenopus and mammalian cardiogenesis, and provide an overview of well-studied cardiac genes in Xenopus, which have been associated with congenital heart conditions. Additionally, we highlight advantages of modeling candidate genes derived from genome wide association studies (GWAS) in Xenopus and discuss commonly used techniques. PMID:29367567

SU-F-T-119: Development of Heart Prediction Model to Increase Accuracy of Dose Reconstruction for Radiotherapy Patients

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

Mosher, E; Choi, M; Lee, C

Purpose: To assess individual variation in heart volume and location in order to develop a prediction model of the heart. This heart prediction model will be used to calculate individualized heart doses for radiotherapy patients in epidemiological studies. Methods: Chest CT images for 30 adult male and 30 adult female patients were obtained from NIH Clinical Center. Image-analysis computer programs were used to segment the whole heart and 8 sub-regions and to measure the volume of each sub- region and the dimension of the whole heart. An analytical dosimetry method was used for the 30 adult female patients to estimatemore » mean heart dose during conventional left breast radiotherapy. Results: The average volumes of the whole heart were 803.37 cm{sup 3} (COV 18.8%) and 570.19 cm{sup 3} (COV 18.8%) for adult male and female patients, respectively, which are comparable with the international reference volumes of 807.69 cm{sup 3} for males and 596.15 cm{sup 3} for females. Some patient characteristics were strongly correlated (R{sup 2}>0.5) with heart volume and heart dimensions (e.g., Body Mass Index vs. heart depth in males: R{sup 2}=0.54; weight vs. heart width in the adult females: R{sup 2}=0.63). We found that the mean heart dose 3.805 Gy (assuming prescribed dose of 50 Gy) in the breast radiotherapy simulations of the 30 adult females could be an underestimate (up to 1.6-fold) or overestimate (up to 1.8-fold) of the patient-specific heart dose. Conclusion: The study showed the significant variation in patient heart volumes and dimensions, resulting in substantial dose errors when a single average heart model is used for retrospective dose reconstruction. We are completing a multivariate analysis to develop a prediction model of the heart. This model will increase accuracy in dose reconstruction for radiotherapy patients and allow us to individualize heart dose calculations for patients whose CT images are not available.« less

Newborn Hypoxia/Anoxia Inhibits Cardiomyocyte Proliferation and Decreases Cardiomyocyte Endowment in the Developing Heart: Role of Endothelin-1

PubMed Central

Paradis, Alexandra N.; Gay, Maresha S.; Wilson, Christopher G.; Zhang, Lubo

2015-01-01

In the developing heart, cardiomyocytes undergo terminal differentiation during a critical window around birth. Hypoxia is a major stress to preterm infants, yet its effect on the development and maturation of the heart remains unknown. We tested the hypothesis in a rat model that newborn anoxia accelerates cardiomyocyte terminal differentiation and results in reduced cardiomyocyte endowment in the developing heart via an endothelin-1-dependent mechanism. Newborn rats were exposed to anoxia twice daily from postnatal day 1 to 3, and hearts were isolated and studied at postnatal day 4 (P4), 7 (P7), and 14 (P14). Anoxia significantly increased HIF-1α protein expression and pre-proET-1 mRNA abundance in P4 neonatal hearts. Cardiomyocyte proliferation was significantly decreased by anoxia in P4 and P7, resulting in a significant reduction of cardiomyocyte number per heart weight in the P14 neonates. Furthermore, the expression of cyclin D2 was significantly decreased due to anoxia, while p27 expression was increased. Anoxia has no significant effect on cardiomyocyte binucleation or myocyte size. Consistently, prenatal hypoxia significantly decreased cardiomyocyte proliferation but had no effect on binucleation in the fetal heart. Newborn administration of PD156707, an ETA-receptor antagonist, significantly increased cardiomyocyte proliferation at P4 and cell size at P7, resulting in an increase in the heart to body weight ratio in P7 neonates. In addition, PD156707 abrogated the anoxia-mediated effects. The results suggest that hypoxia and anoxia via activation of endothelin-1 at the critical window of heart development inhibits cardiomyocyte proliferation and decreases myocyte endowment in the developing heart, which may negatively impact cardiac function later in life. PMID:25692855

Mapping Heart Development in Flies: Src42A Acts Non-Autonomously to Promote Heart Tube Formation in Drosophila

PubMed Central

Vanderploeg, Jessica; Jacobs, J. Roger

2017-01-01

Congenital heart defects, clinically identified in both small and large animals, are multifactorial and complex. Although heritable factors are known to have a role in cardiovascular disease, the full genetic aetiology remains unclear. Model organism research has proven valuable in providing a deeper understanding of the essential factors in heart development. For example, mouse knock-out studies reveal a role for the Integrin adhesion receptor in cardiac tissue. Recent research in Drosophila melanogaster (the fruit fly), a powerful experimental model, has demonstrated that the link between the extracellular matrix and the cell, mediated by Integrins, is required for multiple aspects of cardiogenesis. Here we test the hypothesis that Integrins signal to the heart cells through Src42A kinase. Using the powerful genetics and cell biology analysis possible in Drosophila, we demonstrate that Src42A acts in early events of heart tube development. Careful examination of mutant heart tissue and genetic interaction data suggests that Src42A’s role is independent of Integrin and the Integrin-related Focal Adhesion Kinase. Rather, Src42A acts non-autonomously by promoting programmed cell death of the amnioserosa, a transient tissue that neighbors the developing heart. PMID:29056682

Metabolic circadian rhythms in embryonic turtles.

PubMed

Loudon, Fiona Kay; Spencer, Ricky-John; Strassmeyer, Alana; Harland, Karen

2013-07-01

Oviparous species are model organisms for investigating embryonic development of endogenous physiological circadian rhythms without the influence of maternal biorhythms. Recent studies have demonstrated that heart rates and metabolic rates of embryonic turtles are not constant or always maximal and can be altered in response to the presence of embryos at a more advanced stage of development within the nest. A first step in understanding the physiological mechanisms underpinning these responses in embryonic ectothermic organisms is to develop metabolic profiles (e.g., heart rate) at different temperatures throughout incubation. Heart beat and rhythmic patterns or changes in development may represent important signals or cues within a nest and may be vital to coordinate synchronous hatching well in advance of the final stages of incubation. We developed baseline embryonic heart-rate profiles of embryos of the short-necked Murray River turtle (Emydura macquarii) to determine the stage of embryogenesis that metabolic circadian rhythms become established, if at all. Eggs were incubated at constant temperatures (26°C and 30°C) and heart rates were monitored at 6-h intervals over 24 h every 7-11 days until hatching. Circadian heart rate rhythms were detected at the mid-gestation period and were maintained until hatching. Heart rates throughout the day varied by up to 20% over 24 h and were not related to time of day. This study demonstrated that endogenous metabolic circadian rhythms in developing embryos in turtle eggs establish earlier in embryogenesis than those documented in other vertebrate taxa during embryogenesis. Early establishment of circadian rhythms in heart rates may be critical for communication among embryos and synchrony in hatching and emergence from the nest.

Improving awareness, knowledge and heart-related lifestyle of coronary heart disease among working population through a mHealth programme: study protocol.

PubMed

Wang, Wenru; Zhang, Hui; Lopez, Violeta; Wu, Vivien Xi; Poo, Danny Chiang Choon; Kowitlawakul, Yanika

2015-09-01

To develop a mHealth programme, entitled 'Care4Heart' for the working population in Singapore and thereafter examine its feasibility and effectiveness in increasing the awareness and knowledge of coronary heart disease and improving their heart-related lifestyle. Teaching and encouraging the working population to adopt a healthier lifestyle could result in preventing and/or decreasing the incidence of coronary heart disease among this population. The use of mobile application (app) is the next logical wave of healthcare support tools to prevent and manage chronic diseases like coronary heart disease. A quasi-experimental longitudinal study design. The study will be conducted in a tertiary university in Singapore. A non-probability, quota sampling of 200 participants will be recruited including 100 academic and research staff, 50 administrative staff and 50 support staff and business owners. Once consent is obtained, the newly developed mobile app will be installed onto the participants' smartphones and a well-trained research assistant will brief the participant on the use of the app. The main outcomes will be measured using the survey questionnaires: Awareness of coronary heart disease, Heart Disease Fact Questionnaire-2, Behavioural Risk Factor Surveillance System and Perceived Stress Scale. Data will be collected at baseline and at the 4th week and 6th month thereafter. If this project is successful, Care4Heart - a mHealth and novel prevention educational programme for the working population in Singapore - can be used to promote knowledge and positive heart-related lifestyle changes to prevent coronary heart disease. © 2015 John Wiley & Sons Ltd.

Live dynamic analysis of the developing cardiovascular system in mice

NASA Astrophysics Data System (ADS)

Lopez, Andrew L.; Wang, Shang; Larin, Kirill V.; Larina, Irina V.

2017-02-01

The study of the developing cardiovascular system in mice is important for understanding human cardiogenesis and congenital heart defects. Our research focuses on imaging early development in the mouse embryo to specifically understand cardiovascular development under the regulation of dynamic factors like contractile force and blood flow using optical coherence tomography (OCT). We have previously developed an OCT based approach that combines static embryo culture and advanced image processing with computational modeling to live-image mouse embryos and obtain 4D (3D+time) cardiodynamic datasets. Here we present live 4D dynamic blood flow imaging of the early embryonic mouse heart in correlation with heart wall movement. We are using this approach to understand how specific mutations impact heart wall dynamics, and how this influences flow patterns and cardiogenesis. We perform studies in mutant embryos with cardiac phenotypes such as myosin regulatory light chain 2, atrial isoform (Mlc2a). This work is brings us closer to understanding the connections between dynamic mechanical factors and gene programs responsible for early cardiovascular development.

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

PubMed Central

Ivanovitch, Kenzo; Temiño, Susana

2017-01-01

During vertebrate heart development, two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development. PMID:29202929

4D Subject-Specific Inverse Modeling of the Chick Embryonic Heart Outflow Tract Hemodynamics

PubMed Central

Goenezen, Sevan; Chivukula, Venkat Keshav; Midgett, Madeline; Phan, Ly; Rugonyi, Sandra

2015-01-01

Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography (OCT), we generated 4D (3D + time) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse-method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by less than 15% at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in depth quantitative study of how blood flow influences cardiac development. PMID:26361767

Vitamin D receptor signaling is required for heart development in zebrafish embryo

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

Kwon, Hye-Joo, E-mail: hjkwon@pnu.edu.sa; Biology Department, Princess Nourah University, Riyadh 11671

Vitamin D has been found to be associated with cardiovascular diseases. However, the role of vitamin D in heart development during embryonic period is largely unknown. Vitamin D induces its genomic effects through its nuclear receptor, the vitamin D receptor (VDR). The present study investigated the role of VDR on heart development by antisense-mediated knockdown approaches in zebrafish model system. In zebrafish embryos, two distinct VDR genes (vdra and vdrb) have been identified. Knockdown of vdra has little effect on heart development, whereas disrupting vdrb gene causes various cardiac phenotypes, characterized by pericardial edema, slower heart rate and laterality defects.more » Depletion of both vdra and vdrb (vdra/b) produce additive, but not synergistic effects. To determine whether atrioventricular (AV) cardiomyocytes are properly organized in these embryos, the expression of bmp4, which marks the developing AV boundary at 48 h post-fertilization, was examined. Notably, vdra/b-deficient embryos display ectopic expression of bmp4 towards the ventricle or throughout atrial and ventricular chambers. Taken together, these results suggest that VDR signaling plays an essential role in heart development. - Highlights: • VDR signaling is involved in embryonic heart development. • Knockdown of vdrb, but not vdra, causes decreased heart rate in zebrafish embryo. • Loss of vdr results in cardiac laterality defects. • Loss of vdra/b alters atrioventricular boundary formation. • Loss of vdra/b causes abnormal cardiac looping.« less

Development of Fourier domain optical coherence tomography for applications in developmental biology

NASA Astrophysics Data System (ADS)

Davis, Anjul Maheshwari

Developmental biology is a field in which explorations are made to answer how an organism transforms from a single cell to a complex system made up of trillions of highly organized and highly specified cells. This field, however, is not just for discovery, it is crucial for unlocking factors that lead to diseases, defects, or malformations. The one key ingredient that contributes to the success of studies in developmental biology is the technology that is available for use. Optical coherence tomography (OCT) is one such technology. OCT fills a niche between the high resolution of confocal microscopy and deep imaging penetration of ultrasound. Developmental studies of the chicken embryo heart are of great interest. Studies in mature hearts, zebrafish animal models, and to a more limited degree chicken embryos, indicate a relationship between blood flow and development. It is believed that at the earliest stages, when the heart is still a tube, the purpose of blood flow is not for convective transport of oxygen, nutrients and waster, bur rather to induce shear-related gene expressions to induce further development. Yet, to this date, the simple question of "what makes blood flow?" has not been answered. This is mainly due limited availability to adequate imaging and blood flow measurement tools. Earlier work has demonstrated the potential of OCT for use in studying chicken embryo heart development, however quantitative measurement techniques still needed to be developed. In this dissertation I present technological developments I have made towards building an OCT system to study chick embryo heart development. I will describe: (1) a swept-source OCT with extended imaging depth; (2) a spectral domain OCT system for non-invasive small animal imaging; (3) Doppler flow imaging and techniques for quantitative blood flow measurement in living chicken embryos; and (4) application of the OCT system that was developed in the Specific Aims 2-5 to test hypotheses generated by a finite element model which treats the embryonic chick heart tube as a modified peristaltic pump.

Temporal cohesion of the structural, functional and molecular characteristics of the developing zebrafish heart.

PubMed

Matrone, Gianfranco; Wilson, Kathryn S; Mullins, John J; Tucker, Carl S; Denvir, Martin A

2015-06-01

Heart formation is a complex, dynamic and highly coordinated process of molecular, morphogenetic and functional factors with each interacting and contributing to formation of the mature organ. Cardiac abnormalities in early life can be lethal in mammals but not in the zebrafish embryo which has been widely used to study the developing heart. While early cardiac development in the zebrafish has been well characterized, functional changes during development and how these relate to architectural, cellular and molecular aspects of development have not been well described previously. To address this we have carefully characterised cardiac structure, function, cardiomyocyte proliferation and cardiac-specific gene expression between 48 and 120 hpf in the zebrafish. We show that the zebrafish heart increases in volume and changes shape significantly between 48 and 72 hpf accompanied by a 40% increase in cardiomyocyte number. Between 96 and 120 hpf, while external heart expansion slows, there is rapid formation of a mature and extensive trabecular network within the ventricle chamber. While ejection fraction does not change during the course of development other determinants of contractile function increase significantly particularly between 72 and 96 hpf leading to an increase in cardinal vein blood flow. This study has revealed a number of novel aspects of cardiac developmental dynamics with striking temporal orchestration of structure and function within the first few days of development. These changes are associated with changes in expression of developmental and maturational genes. This study provides important insights into the complex temporal relationship between structure and function of the developing zebrafish heart. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Capturing structure and function in an embryonic heart with biophotonic tools

PubMed Central

Karunamuni, Ganga H.; Gu, Shi; Ford, Matthew R.; Peterson, Lindsy M.; Ma, Pei; Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Disturbed cardiac function at an early stage of development has been shown to correlate with cellular/molecular, structural as well as functional cardiac anomalies at later stages culminating in the congenital heart defects (CHDs) that present at birth. While our knowledge of cellular and molecular steps in cardiac development is growing rapidly, our understanding of the role of cardiovascular function in the embryo is still in an early phase. One reason for the scanty information in this area is that the tools to study early cardiac function are limited. Recently developed and adapted biophotonic tools may overcome some of the challenges of studying the tiny fragile beating heart. In this chapter, we describe and discuss our experience in developing and implementing biophotonic tools to study the role of function in heart development with emphasis on optical coherence tomography (OCT). OCT can be used for detailed structural and functional studies of the tubular and looping embryo heart under physiological conditions. The same heart can be rapidly and quantitatively phenotyped at early and again at later stages using OCT. When combined with other tools such as optical mapping (OM) and optical pacing (OP), OCT has the potential to reveal in spatial and temporal detail the biophysical changes that can impact mechanotransduction pathways. This information may provide better explanations for the etiology of the CHDs when interwoven with our understanding of morphogenesis and the molecular pathways that have been described to be involved. Future directions for advances in the creation and use of biophotonic tools are discussed. PMID:25309451

Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth.

PubMed

Yu, Pujiao; Wang, Hongbao; Xie, Yuan; Zhou, Jinzhe; Yao, Jianhua; Che, Lin

2016-01-01

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs-miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p-were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

Heart failure patients' attitudes, beliefs, expectations and experiences of self-management strategies: a qualitative synthesis.

PubMed

Wingham, Jennifer; Harding, Geoff; Britten, Nicky; Dalal, Hayes

2014-06-01

To develop a model of heart failure patients' attitudes, beliefs, expectations, and experiences based on published qualitative research that could influence the development of self-management strategies. A synthesis of 19 qualitative research studies using the method of meta-ethnography. This synthesis offers a conceptual model of the attitudes, beliefs, and expectations of patients with heart failure. Patients experienced a sense of disruption before developing a mental model of heart failure. Patients' reactions included becoming a strategic avoider, a selective denier, a well-intentioned manager, or an advanced self-manager. Patients responded by forming self-management strategies and finally assimilated the strategies into everyday life seeking to feel safe. This conceptual model suggests that there are a range of interplaying factors that facilitate the process of developing self-management strategies. Interventions should take into account patients' concepts of heart failure and their subsequent reactions.

Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

PubMed

Chruscinski, Andrzej; Huang, Flora Y Y; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C; Kozuszko, Stella; Tinckam, Kathryn J; Rao, Vivek; Dunn, Shannon E; Persinger, Michael A; Levy, Gary A; Ross, Heather J

2016-01-01

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR.

Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation

PubMed Central

Chruscinski, Andrzej; Huang, Flora Y. Y.; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C.; Kozuszko, Stella; Tinckam, Kathryn J.; Rao, Vivek; Dunn, Shannon E.; Persinger, Michael A.; Levy, Gary A.; Ross, Heather J.

2016-01-01

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR. PMID:26967734

Detection of a ventricular-specific myosin heavy chain in adult and developing chicken heart

PubMed Central

1986-01-01

In the present study, a monoclonal antibody (McAb), ALD19, generated against myosin of slow tonic muscle, was shown to react with the heavy chain of ventricular myosin in the adult chicken heart. With this antibody, it was possible to detect a ventricular-specific myosin during myocardial differentiation and to show that the epitope recognized by ALD19 was present from the earliest stages of ventricular differentiation and maintained throughout development only in the ventricle. A second McAb, specific for atrial myosin heavy chain (MHC) (Gonzalez-Sanchez, A., and D. Bader, 1984, Dev. Biol., 103:151-158), was used as a control to detect an atrial-specific myosin in the caudal portion of the developing heart at Hamburger-Hamilton stage 15. It was found that the appearance of ventricular MHC predated the expression of atrial MHC by approximately 1 d in ovo and that specific MHCs were always differentially distributed. While a common primordial MHC may be present in the early heart, this study showed the tissue-specific expression of a ventricular MHC during the initial stages of heart development and its differential accumulation throughout development. PMID:3514633

Biphasic Allometry of Cardiac Growth in the Developing Kangaroo Macropus fuliginosus.

PubMed

Snelling, Edward P; Taggart, David A; Maloney, Shane K; Farrell, Anthony P; Seymour, Roger S

2015-01-01

Interspecific studies of adult mammals show that heart mass (M(h), g) increases in direct proportion to body mass (M(b), kg), such that M(h) ∝ M(b)(1.00). However, intraspecific studies on heart mass in mammals at different stages of development reveal considerable variation between species, M(h) ∝ M(b)(0.70-1.00). Part of this variation may arise as a result of the narrow body size range of growing placental mammals, from birth to adulthood. Marsupial mammals are born relatively small and offer an opportunity to examine the ontogeny of heart mass over a much broader body size range. Data from 29 western grey kangaroos Macropus fuliginosus spanning 800-fold in body mass (0.084-67.5 kg) reveal the exponent for heart mass decreases significantly when the joey leaves the pouch (ca. 5-6 kg body mass). In the pouch, the heart mass of joeys scales with hyperallometry, M(h(in-pouch)) = 6.39 M(b)(1.10 ± 0.05), whereas in free-roaming juveniles and adults, heart mass scales with hypoallometry, M(h(postpouch)) = 14.2 Mb(0.77 ± 0.08). Measurements of heart height, width, and depth support this finding. The relatively steep heart growth allometry during in-pouch development is consistent with the increase in relative cardiac demands as joeys develop endothermy and the capacity for hopping locomotion. Once out of the pouch, the exponent decreases sharply, possibly because the energy required for hopping is independent of speed, and the efficiency of energy storage during hopping increases as the kangaroo grows. The right:left ventricular mass ratios (0.30-0.35) do not change over the body mass range and are similar to those of other mammals, reflecting the principle of Laplace for the heart.

Development and evaluation of a dietary self-management programme for older adults with low literacy and heart disease: pilot study of feasibility and acceptability.

PubMed

Shao, Jung-Hua; Chen, Su-Hui

2016-12-01

To develop a dietary self-management programme for salt-, fluid-, fat- and cholesterol-intake behaviours for older adults with low literacy and heart disease and evaluate the feasibility and acceptability of the programme. Eating behaviours such as fluid, salt, fat and cholesterol intake are an important factor related to heart disease outcomes. People with low literacy have difficulty following recommended health behaviours, but limited research has investigated intervention programmes for this population. Programme development and pilot testing its feasibility and acceptability. Recommendations were also collected from participants and the research assistant for future large-scale interventions. The study had two phases. Phase I consisted of programme development based on previous qualitative findings, a systematic review of the literature, clinical practice experience and expert opinion. In Phase II, we pilot tested the programme from January - June 2014 in a convenience sample of 10 older adults with low literacy, heart disease and recruited from a medical centre in northern Taiwan. Pilot testing showed that our programme was feasible and acceptable to older adults with low literacy and heart disease. Moreover, the final version of the programme was revised based on participants' and the research assistant's recommendations. Our study results suggest that with guidance and assistance, older adults with low literacy and heart disease can be motivated to take action for their health and are empowered by learning how to self-manage their heart-healthy eating behaviours. © 2016 John Wiley & Sons Ltd.

Expression analysis of Baf60c during heart regeneration in axolotls and neonatal mice.

PubMed

Nakamura, Ryo; Koshiba-Takeuchi, Kazuko; Tsuchiya, Megumi; Kojima, Mizuyo; Miyazawa, Asuka; Ito, Kohei; Ogawa, Hidesato; Takeuchi, Jun K

2016-05-01

Some organisms, such as zebrafish, urodele amphibians, and newborn mice, have a capacity for heart regeneration following injury. However, adult mammals fail to regenerate their hearts. To know why newborn mice can regenerate their hearts, we focused on epigenetic factors, which are involved in cell differentiation in many tissues. Baf60c (BRG1/BRM-associated factor 60c), a component of ATP-dependent chromatin-remodeling complexes, has an essential role for cardiomyocyte differentiation at the early heart development. To address the function of Baf60c in postnatal heart homeostasis and regeneration, we examined the detailed expression/localization patterns of Baf60c in both mice and axolotls. In the mouse heart development, Baf60c was highly expressed in the entire heart at the early stages, but gradually downregulated at the postnatal stages. During heart regeneration in neonatal mice and axolotls, Baf60c expression was strongly upregulated after resection. Interestingly, the timing of Baf60c upregulation after resection was consistent with the temporal dynamics of cardiomyocyte proliferation. Moreover, knockdown of Baf60c downregulated proliferation of neonatal mouse cardiomyocytes. These data suggested that Baf60c plays an important role in cardiomyocyte proliferation in heart development and regeneration. This is the first study indicating that Baf60c contributes to the heart regeneration in vertebrates. © 2016 Japanese Society of Developmental Biologists.

History of Right Heart Catheterization: 100 Years of Experimentation and Methodology Development

PubMed Central

Nossaman, Bobby D.; Scruggs, Brittni A.; Nossaman, Vaughn E.; Murthy, Subramanyam N.; Kadowitz, Philip J.

2010-01-01

The development of right heart catheterization has provided the clinician the ability to diagnose patients with congenital and acquired right heart disease, and to monitor patients in the ICU with significant cardiovascular illnesses. The development of bedside pulmonary artery catheterization has become a standard of care for the critically ill patient since its introduction into the ICU almost 40 years ago. However, adoption of this procedure into the mainstream of clinical practice occurred without prior evaluation or demonstration of its clinical or cost-effectiveness. Moreover, current randomized, controlled trials provide little evidence in support of the clinical utility of pulmonary artery catheterization in the management of critically ill patients. Nevertheless, the right heart catheter is an important diagnostic tool to assist the clinician in the diagnosis of congenital heart disease and acquired right heart disease, and moreover, when catheter placement is proximal to the right auricle (atria), this catheter provides an important and safe route for administration of fluids, medications, and parenteral nutrition. The purpose of this manuscript is to review the development of right heart catheterization that led to the ability to conduct physiologic studies in cardiovascular dynamics in normal individuals and in patients with cardiovascular diseases, and to review current controversies of the extension of the right heart catheter, the pulmonary artery catheter. PMID:20160536

Nursing Care Hour Standards Study. Part 1. Section A. Patient Classification System Model Development

DTIC Science & Technology

1981-09-01

Change = 2311 (257) Teaching - Diabetic = 2313 (258) Labor Room Examination and Preparation, Routine = 2434 (259) Fetal Heart Tones, Manual = 2412 (260... Fetal Heart Tones, Doppler = 2413 (261) Dilatation and Effecement Assessment = 2403 (262) Dilatation and Effacement Assessment, Assisting Physician...Ultrasonic Transducer/Tocotransducer = 2435 (270) Monitoring Fetal Heart Tones, Ultrasonic Transducer = 2436 (271) Monitoring Fetal Heart Tones, Ultrasonic

Modulations of Heart Rate, ECG, and Cardio-Respiratory Coupling Observed in Polysomnography

PubMed Central

Penzel, Thomas; Kantelhardt, Jan W.; Bartsch, Ronny P.; Riedl, Maik; Kraemer, Jan F.; Wessel, Niels; Garcia, Carmen; Glos, Martin; Fietze, Ingo; Schöbel, Christoph

2016-01-01

The cardiac component of cardio-respiratory polysomnography is covered by ECG and heart rate recordings. However, their evaluation is often underrepresented in summarizing reports. As complements to EEG, EOG, and EMG, these signals provide diagnostic information for autonomic nervous activity during sleep. This review presents major methodological developments in sleep research regarding heart rate, ECG, and cardio-respiratory couplings in a chronological (historical) sequence. It presents physiological and pathophysiological insights related to sleep medicine obtained by new technical developments. Recorded nocturnal ECG facilitates conventional heart rate variability (HRV) analysis, studies of cyclical variations of heart rate, and analysis of ECG waveform. In healthy adults, the autonomous nervous system is regulated in totally different ways during wakefulness, slow-wave sleep, and REM sleep. Analysis of beat-to-beat heart-rate variations with statistical methods enables us to estimate sleep stages based on the differences in autonomic nervous system regulation. Furthermore, up to some degree, it is possible to track transitions from wakefulness to sleep by analysis of heart-rate variations. ECG and heart rate analysis allow assessment of selected sleep disorders as well. Sleep disordered breathing can be detected reliably by studying cyclical variation of heart rate combined with respiration-modulated changes in ECG morphology (amplitude of R wave and T wave). PMID:27826247

Modulations of Heart Rate, ECG, and Cardio-Respiratory Coupling Observed in Polysomnography.

PubMed

Penzel, Thomas; Kantelhardt, Jan W; Bartsch, Ronny P; Riedl, Maik; Kraemer, Jan F; Wessel, Niels; Garcia, Carmen; Glos, Martin; Fietze, Ingo; Schöbel, Christoph

2016-01-01

The cardiac component of cardio-respiratory polysomnography is covered by ECG and heart rate recordings. However, their evaluation is often underrepresented in summarizing reports. As complements to EEG, EOG, and EMG, these signals provide diagnostic information for autonomic nervous activity during sleep. This review presents major methodological developments in sleep research regarding heart rate, ECG, and cardio-respiratory couplings in a chronological (historical) sequence. It presents physiological and pathophysiological insights related to sleep medicine obtained by new technical developments. Recorded nocturnal ECG facilitates conventional heart rate variability (HRV) analysis, studies of cyclical variations of heart rate, and analysis of ECG waveform. In healthy adults, the autonomous nervous system is regulated in totally different ways during wakefulness, slow-wave sleep, and REM sleep. Analysis of beat-to-beat heart-rate variations with statistical methods enables us to estimate sleep stages based on the differences in autonomic nervous system regulation. Furthermore, up to some degree, it is possible to track transitions from wakefulness to sleep by analysis of heart-rate variations. ECG and heart rate analysis allow assessment of selected sleep disorders as well. Sleep disordered breathing can be detected reliably by studying cyclical variation of heart rate combined with respiration-modulated changes in ECG morphology (amplitude of R wave and T wave).

The Impact of Worsening Heart Failure in the United States

PubMed Central

Cooper, Lauren B.; DeVore, Adam D.; Felker, G. Michael

2015-01-01

Synopsis In-hospital worsening heart failure represents a clinical scenario in which a patient hospitalized for treatment of acute heart failure experiences a worsening of their condition while in the hospital, requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and post-discharge outcomes. In-hospital worsening heart failure is increasingly being used as an endpoint, or as part of a combined endpoint, in many clinical trials in acute heart failure. This endpoint has advantages over other endpoints commonly used in acute and chronic heart failure trials, such as dyspnea relief and mortality or rehospitalization. Despite the extensive study of this condition, no treatment strategies have been approved for the prevention of this condition. However, several prediction models have been developed to identify worsening heart failure. Continued study in this area is warranted. PMID:26462100

Domestic and foreign trends in the prevalence of heart failure and the necessity of next-generation artificial hearts: a survey by the Working Group on Establishment of Assessment Guidelines for Next-Generation Artificial Heart Systems.

PubMed

Tatsumi, Eisuke; Nakatani, Takeshi; Imachi, Kou; Umezu, Mitsuo; Kyo, Shun-Ei; Sase, Kazuhiro; Takatani, Setsuo; Matsuda, Hikaru

2007-01-01

A series of guidelines for development and assessment of next-generation medical devices has been drafted under an interagency collaborative project by the Ministry of Health, Labor and Welfare and the Ministry of Economy, Trade and Industry. The working group for assessment guidelines of next-generation artificial hearts reviewed the trend in the prevalence of heart failure and examined the potential usefulness of such devices in Japan and in other countries as a fundamental part of the process of establishing appropriate guidelines. At present, more than 23 million people suffer from heart failure in developed countries, including Japan. Although Japan currently has the lowest mortality from heart failure among those countries, the number of patients is gradually increasing as our lifestyle becomes more Westernized; the associated medical expenses are rapidly growing. The number of heart transplantations, however, is limited due to the overwhelming shortage of donor hearts, not only in Japan but worldwide. Meanwhile, clinical studies and surveys have revealed that the major causes of death in patients undergoing long-term use of ventricular assist devices (VADs) were infection, thrombosis, and mechanical failure, all of which are typical of VADs. It is therefore of urgent and universal necessity to develop next-generation artificial hearts that have excellent durability to provide at least 2 years of event-free operation with a superior quality of life and that can be used for destination therapy to save patients with irreversible heart failure. It is also very important to ensure that an environment that facilitates the development, testing, and approval evaluation processes of next-generation artificial hearts be established as soon as possible.

Wireless patient monitoring system for a moving-actuator type artificial heart.

PubMed

Nam, K W; Chung, J; Choi, S W; Sun, K; Min, B G

2006-10-01

In this study, we developed a wireless monitoring system for outpatients equipped with a moving-actuator type pulsatile bi-ventricular assist device, AnyHeart. The developed monitoring system consists of two parts; a Bluetooth-based short-distance self-monitoring system that can monitor and control the operating status of a VAD using a Bluetooth-embedded personal digital assistant or a personal computer within a distance of 10 meters, and a cellular network-based remote monitoring system that can continuously monitor and control the operating status of AnyHeart at any location. Results of in vitro experiments demonstrate the developed system's ability to monitor the operational status of an implanted AnyHeart.

The Influence of Motor Impairment on Autonomic Heart Rate Modulation among Children with Cerebral Palsy

ERIC Educational Resources Information Center

Zamuner, Antonio Roberto; Cunha, Andrea Baraldi; da Silva, Ester; Negri, Ana Paola; Tudella, Eloisa; Moreno, Marlene Aparecida

2011-01-01

The study of heart rate variability is an important tool for a noninvasive evaluation of the neurocardiac integrity. The present study aims to evaluate the autonomic heart rate modulation in supine and standing positions in 12 children diagnosed with cerebral palsy and 16 children with typical motor development (control group), as well as to…

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.

Zebrafish cardiac development requires a conserved secondary heart field

PubMed Central

Hami, Danyal; Grimes, Adrian C.; Tsai, Huai-Jen; Kirby, Margaret L.

2011-01-01

The secondary heart field is a conserved developmental domain in avian and mammalian embryos that contributes myocardium and smooth muscle to the definitive cardiac arterial pole. This field is part of the overall heart field and its myocardial component has been fate mapped from the epiblast to the heart in both mammals and birds. In this study we show that the population that gives rise to the arterial pole of the zebrafish can be traced from the epiblast, is a discrete part of the mesodermal heart field, and contributes myocardium after initial heart tube formation, giving rise to both smooth muscle and myocardium. We also show that Isl1, a transcription factor associated with undifferentiated cells in the secondary heart field in other species, is active in this field. Furthermore, Bmp signaling promotes myocardial differentiation from the arterial pole progenitor population, whereas inhibiting Smad1/5/8 phosphorylation leads to reduced myocardial differentiation with subsequent increased smooth muscle differentiation. Molecular pathways required for secondary heart field development are conserved in teleosts, as we demonstrate that the transcription factor Tbx1 and the Sonic hedgehog pathway are necessary for normal development of the zebrafish arterial pole. PMID:21558385

Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

PubMed

Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

2017-10-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacists' role in the post-discharge management of patients with heart failure: a literature review.

PubMed

Ponniah, A; Anderson, B; Shakib, S; Doecke, C J; Angley, M

2007-08-01

The incidence of heart failure is increasing in developed countries. In the aged population, heart failure is a common cause of hospitalization and hospital readmission, which in conjunction with post-discharge care, impose a significant cost burden. Inappropriate medication management and drug-related problems have been identified as major contributors to hospital readmissions. In order to enhance the care and clinical outcomes, and reduce treatment costs, heart failure disease management programmes (DMPs) have been developed. It is recommended that these programmes adopt a multi-disciplinary approach, and pharmacists, with their understanding and knowledge of medication management, can play a vital role in the post-discharge care of heart failure patients. The aim of this literature review was to assess the role of pharmacists in the provision of post-charge services for heart failure patients. An extensive literature search was undertaken to identify published studies and review articles evaluating the benefits of an enhanced medication management service for patients with heart failure post-discharge. Seven studies were identified evaluating 'outpatient' or 'post-discharge' pharmacy services for patients with heart failure. In three studies, services were delivered prior to discharge with either subsequent telephone or home visit follow-up. Three studies involved the role of a pharmacist in a specialist heart failure outpatient clinic. One study focused on a home-based intervention. In six of these studies, positive outcomes, such as decreases in unplanned hospital readmissions, death rates and greater compliance and medication knowledge were demonstrated. One study did not show any difference in the number of hospitalizations between intervention and control groups. The quality of evidence of the randomized controlled trials was assessed using the Jadad scoring method. None of the studies achieved a score of more than 2, out of a maximum of 5, indicating the potential for bias. The DMPs carried out by pharmacists have contributed to positive patient outcomes, which has highlighted the value of extending the traditional roles of pharmacists from the provision of professional guidance to the delivery of continuity of care through a more holistic and direct approach. This review has demonstrated the effectiveness of pharmacists' interventions to reduce the morbidity and mortality associated with heart failure. However, there is an on-going need for the development and evaluation of pharmacy services for these patients.

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.

Mechanical regulation of cardiac development

PubMed Central

Lindsey, Stephanie E.; Butcher, Jonathan T.; Yalcin, Huseyin C.

2014-01-01

Mechanical forces are essential contributors to and unavoidable components of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development. PMID:25191277

Effects of electromagnetic field exposure on the heart: a systematic review.

PubMed

Elmas, Onur

2016-01-01

The use of electrical devices has gradually increased throughout the last century, and scientists have suggested that electromagnetic fields (EMF) generated by such devices may have harmful effects on living creatures. This work represents a systematic review of collective scholarly literature examining the effects of EMFs on the heart. Although most works describing effects of EMF exposure have been carried out using city electric frequencies (50-60 Hz), a consensus has not been reached about whether long- or short-term exposure to 50-60 Hz EMF negatively affects the heart. Studies have indicated that EMFs produced at cell-phone frequencies cause no-effect on the heart. Differences between results of studies may be due to a compensatory response developed by the body over time. At greater EMF strengths or shorter exposures, the ability of the body to develop compensation mechanisms is reduced and the potential for heart-related effects increases. It is noteworthy that diseases of heart tissues such as myocardial ischemia can also be successfully treated using EMF. Despite the substantial volume of data that has been collected on heart-related effects of EMFs, additional studies are needed at the cellular and molecular level to fully clarify the subject. Until the effects of EMF on heart tissue are more fully explored, electronic devices generating EMFs should be approached with caution. © The Author(s) 2013.

Assessment of the role of copy-number variants in 150 patients with congenital heart defects.

PubMed

Derwińska, Katarzyna; Bartnik, Magdalena; Wiśniowiecka-Kowalnik, Barbara; Jagła, Mateusz; Rudziński, Andrzej; Pietrzyk, Jacek J; Kawalec, Wanda; Ziółkowska, Lidia; Kutkowska-Kaźmierczak, Anna; Gambin, Tomasz; Sykulski, Maciej; Shaw, Chad A; Gambin, Anna; Mazurczak, Tadeusz; Obersztyn, Ewa; Bocian, Ewa; Stankiewicz, Paweł

2012-01-01

Congenital heart defects are the most common group of major birth anomalies and one of the leading causes of infant deaths. Mendelian and chromosomal syndromes account for about 20% of congenital heart defects and in some cases are associated with other malformations, intellectual disability, and/or dysmorphic features. The remarkable conservation of genetic pathways regulating heart development in animals suggests that genetic factors can be responsible for a significantly higher percentage of cases. Assessment of the role of CNVs in the etiology of congenital heart defects using microarray studies. Genome-wide array comparative genomic hybridization, targeting genes known to play an important role in heart development or responsible for abnormal cardiac phenotype was used in the study on 150 patients. In addition, we have used multiplex ligation-dependent probe amplification specific for chromosome 22q11.2 region. We have identified 21 copy-number variants, including 13 known causative recurrent rearrangements (12 deletions 22q11.2 and one deletion 7q11.23), three potentially pathogenic duplications (5q14.2, 15q13.3, and 22q11.2), and five variants likely benign for cardiac anomalies. We suggest that abnormal copy-number of the ARRDC3 and KLF13 genes can be responsible for heart defects. Our study demonstrates that array comparative genomic hybridization enables detection of clinically significant chromosomal imbalances in patients with congenital heart defects.

Artificial heart for humanoid robot

NASA Astrophysics Data System (ADS)

Potnuru, Akshay; Wu, Lianjun; Tadesse, Yonas

2014-03-01

A soft robotic device inspired by the pumping action of a biological heart is presented in this study. Developing artificial heart to a humanoid robot enables us to make a better biomedical device for ultimate use in humans. As technology continues to become more advanced, the methods in which we implement high performance and biomimetic artificial organs is getting nearer each day. In this paper, we present the design and development of a soft artificial heart that can be used in a humanoid robot and simulate the functions of a human heart using shape memory alloy technology. The robotic heart is designed to pump a blood-like fluid to parts of the robot such as the face to simulate someone blushing or when someone is angry by the use of elastomeric substrates and certain features for the transport of fluids.

Development of the Jackson Heart Study Coordinating Center

PubMed Central

Campbell-Jenkins, Brenda W.; Addison, Clifton C.; Young, Lavon; Anugu, Pramod; Wilson, Gregory; Sarpong, Daniel

2009-01-01

The public health burden caused by cardiovascular disease (CVD) continues to adversely affect individuals in terms of cost, life expectancy, medical, pharmaceutical and hospital care. This burden has been excessive in the case of African Americans. The objective of this paper is to chronicle the procedures and processes that were implemented in the development of the Jackson Heart Study Coordinating Center. The Jackson Heart Study (JHS) is a population-based investigation of traditional and emerging risk factors that predict progression to CVD among African Americans. In response to the struggle against CVD, the Jackson Heart Study has convened a professional, technical, and administrative staff with specific competence in the operation of a coordinating center to handle the wide variety of areas related to CVD studies. The Jackson Heart Study Coordinating Center (JHSCC) was created to assure validity of the JHS findings and provide the resources necessary to meet comprehensive statistical needs (planning, implementing and monitoring data analysis); data management (designing, implementing and managing data collection and quality control), and administrative support. The JHSCC began with a commitment to support study functions in order to increase participant recruitment, retention and safety, meet regulatory requirements, prepare progress reports, and facilitate effective communication with the community and between all JHS centers. The JHSCC facilitates the efforts of the JHS scientists through the development and implementation of the study protocol. The efforts of the JHSCC have resulted in the successful preparation of scientific reports and manuscripts for publication and presentation of study findings and results. In summary, the JHSCC has emerged as an effective research mechanism that serves as the driving force behind the Jackson Heart Study activities. PMID:19543408

The progressive onset of cholinergic and adrenergic control of heart rate during development in the green iguana, Iguana iguana.

PubMed

Sartori, Marina R; Leite, Cleo A C; Abe, Augusto S; Crossley, Dane A; Taylor, Edwin W

2015-10-01

The autonomic control of heart rate was studied throughout development in embryos of the green iguana, Iguana iguana by applying receptor agonists and antagonists of the parasympathetic and sympathetic systems. Acetylcholine (Ach) slowed or stopped the heart and atropine antagonized the response to Ach indicating the presence of muscarinic cholinoceptors on the heart of early embryos. However, atropine injections had no impact on heart rate until immediately before hatching, when it increased heart rate by 15%. This cholinergic tonus increased to 34% in hatchlings and dropped to 24% in adult iguanas. Although epinephrine was without effect, injection of propranolol slowed the heart throughout development, indicating the presence of β-adrenergic receptors on the heart of early embryos, possibly stimulated by high levels of circulating catecholamines. The calculated excitatory tonus varied between 33% and 68% until immediately before hatching when it fell to 25% and 29%, a level retained in hatchlings and adults. Hypoxia caused a bradycardia in early embryos that was unaffected by injection of atropine indicating that hypoxia has a direct effect upon the heart. In later embryos and hatchlings hypoxia caused a tachycardia that was unaffected by injection of atropine. Subsequent injection of propranolol reduced heart rate both uncovering a hypoxic bradycardia in late embryos and abolishing tachycardia in hatchlings. Hypercapnia was without effect on heart rate in late stage embryos and in hatchlings. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypoplastic left heart syndrome (image)

MedlinePlus

Hypoplastic left heart syndrome is a congenital heart condition that occurs during the development of the heart in the ... womb. During the heart's development, parts of the left side of the heart (mitral valve, left ventricle ...

Neonatal Lipopolysaccharide Exposure Gender-Dependently Increases Heart Susceptibility to Ischemia/Reperfusion Injury in Male Rats.

PubMed

Zhang, Peng; Lv, Juanxiu; Li, Yong; Zhang, Lubo; Xiao, Daliao

2017-01-01

Background: Adverse stress exposure during the early neonatal period has been shown to cause aberrant development, resulting in an increased risk of adult disease. We tested the hypothesis that neonatal exposure to lipopolysaccharide (LPS) does not alter heart function at rest condition but causes heart dysfunction under stress stimulation later in life. Methods: Saline control or LPS were administered to neonatal rats via intraperitoneal injection. Experiments were conducted in 6 week-old male and female rats. Isolated hearts were perfused in a Langendorff preparation. Results: Neonatal LPS exposure exhibited no effects on the body weight of the developing rats, but induced decreases in the left ventricle (LV) to the body weight ratio in male rats. Neonatal LPS exposure showed no effects on the baseline heart function determined by in vivo and ex vivo experiments, but caused decreases in the post-ischemic recovery of the LV function in male but not female rats. Neonatal LPS-mediated LV dysfunction was associated with an increase in myocardial infarct size and the LDH release in the male rats. Conclusion: The present study provides novel evidence that neonatal immune challenges could induce gender-dependent long-term effects on cardiac development and heart function, which reinforces the notion that adverse stress exposure during the early neonatal period can aggravate heart functions and the development of a heart ischemia-sensitive phenotype later in life.

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

PubMed

Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Tena, Juan J; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F; Roy, Anna R; Galjart, Niels; Delgado-Olguin, Paul; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis; Manzanares, Miguel

2017-08-01

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

PubMed Central

Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F.; Roy, Anna R.; Galjart, Niels; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis

2017-01-01

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development. PMID:28846746

Imaging of cardiovascular dynamics in early mouse embryos with swept source optical coherence tomography

NASA Astrophysics Data System (ADS)

Larina, Irina V.; Liebling, Michael; Dickinson, Mary E.; Larin, Kirill V.

2009-02-01

Congenital cardiovascular defects are very common, occurring in 1% of live births, and cardiovascular failures are the leading cause of birth defect-related deaths in infants. To improve diagnostics, prevention and treatment of cardiovascular abnormalities, we need to understand not only how cells form the heart and vessels but also how physical factors such as heart contraction and blood flow influence heart development and changes in the circulatory network. Mouse models are an excellent resource for studying cardiovascular development and disease because of the resemblance to humans, rapid generation time, and availability of mutants with cardiovascular defects linked to human diseases. In this work, we present results on development and application of Doppler Swept Source Optical Coherence Tomography (DSS-OCT) for imaging of cardiovascular dynamics and blood flow in the mouse embryonic heart and vessels. Our studies demonstrated that the spatial and temporal resolution of the DSS-OCT makes it possible to perform sensitive measurements of heart and vessel wall movements and to investigate how contractile waves facilitate the movement of blood through the circulatory system.

De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes.

PubMed

Lenihan, Colin R; Liu, Sai; Deswal, Anita; Montez-Rath, Maria E; Winkelmayer, Wolfgang C

2018-03-29

Heart failure is an important cause of morbidity and mortality following kidney transplantation. Some studies in the general population have shown that the incidence of heart failure has decreased during the past 20 years. However, it is not currently known whether such a trend exists in the kidney transplantation population. Retrospective observational cohort study. Adult patients included in the US Renal Data System who underwent their first kidney transplantation in the United States between 1998 and 2010 with at least 6 months of continuous Medicare parts A and B coverage before transplantation and no prior evidence for a diagnosis of heart failure before kidney transplantation. Calendar year of transplantation and calendar year of posttransplantation heart failure diagnosis. De novo posttransplantation heart failure defined using International Classification of Diseases, Ninth Revision diagnosis codes and mortality following de novo posttransplantation heart failure diagnosis. Secular trends in de novo post-kidney transplantation heart failure were examined using Cox proportional hazards analysis. Within a study cohort of 48,771 patients, 7,269 developed de novo heart failure within 3 years of kidney transplantation, with a median time to heart failure of 0.76 years. The adjusted HR for heart failure with death as competing risk comparing patients who underwent transplantation in 2010 with those who underwent transplantation in 1998 was 0.69 (95% CI, 0.60-0.79). No temporal trend in mortality following a diagnosis of post-kidney transplantation heart failure was observed. Potential residual confounding from either incorrectly ascertained or unavailable confounders. The cohort was limited to Medicare beneficiaries. Adjusted for demographic and clinical characteristics, the risk for developing de novo post-kidney transplantation heart failure has declined significantly between 1998 and 2010, with no apparent change in subsequent mortality. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Opdahl, Anders; Venkatesh, Bharath Ambale; Fernandes, Veronica R. S.; Wu, Colin O.; Nasir, Khurram; Choi, Eui-Young; Almeida, Andre L. C.; Rosen, Boaz; Carvalho, Benilton; Edvardsen, Thor; Bluemke, David A.; Lima, Joao A. C.

2014-01-01

OBJECTIVE To investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function is not well described in an asymptomatic multi-ethnic population. METHODS Participants in the Multi-Ethnic Study of Atherosclerosis had resting heart rate measured at inclusion. Incident HF was registered (n=176) during follow-up (median 7 years) in those who underwent cardiac MRI (n=5000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 bpm increase in resting heart rate there was a 4% greater adjusted relative risk for incident HF (Hazard Ratio: 1.04 (1.02, 1.06 (95% CI); P<0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even in analyses when all coronary heart disease events were excluded from the model. CONCLUSION Elevated resting heart rate is associated with increased risk for incident HF in asymptomatic participants in MESA. Higher heart rate is related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. PMID:24412444

Fuzzy Expert System for Heart Attack Diagnosis

NASA Astrophysics Data System (ADS)

Hassan, Norlida; Arbaiy, Nureize; Shah, Noor Aziyan Ahmad; Afizah Afif@Afip, Zehan

2017-08-01

Heart attack is one of the serious illnesses and reported as the main killer disease. Early prevention is significant to reduce the risk of having the disease. The prevention efforts can be strengthen through awareness and education about risk factor and healthy lifestyle. Therefore the knowledge dissemination is needed to play role in order to distribute and educate public in health care management and disease prevention. Since the knowledge dissemination in medical is important, there is a need to develop a knowledge based system that can emulate human intelligence to assist decision making process. Thereby, this study utilized hybrid artificial intelligence (AI) techniques to develop a Fuzzy Expert System for Diagnosing Heart Attack Disease (HAD). This system integrates fuzzy logic with expert system, which helps the medical practitioner and people to predict the risk and as well as diagnosing heart attack based on given symptom. The development of HAD is expected not only providing expert knowledge but potentially become one of learning resources to help citizens to develop awareness about heart-healthy lifestyle.

Heart murmur detection based on wavelet transformation and a synergy between artificial neural network and modified neighbor annealing methods.

PubMed

Eslamizadeh, Gholamhossein; Barati, Ramin

2017-05-01

Early recognition of heart disease plays a vital role in saving lives. Heart murmurs are one of the common heart problems. In this study, Artificial Neural Network (ANN) is trained with Modified Neighbor Annealing (MNA) to classify heart cycles into normal and murmur classes. Heart cycles are separated from heart sounds using wavelet transformer. The network inputs are features extracted from individual heart cycles, and two classification outputs. Classification accuracy of the proposed model is compared with five multilayer perceptron trained with Levenberg-Marquardt, Extreme-learning-machine, back-propagation, simulated-annealing, and neighbor-annealing algorithms. It is also compared with a Self-Organizing Map (SOM) ANN. The proposed model is trained and tested using real heart sounds available in the Pascal database to show the applicability of the proposed scheme. Also, a device to record real heart sounds has been developed and used for comparison purposes too. Based on the results of this study, MNA can be used to produce considerable results as a heart cycle classifier. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparison of Two Instructional Formats on Heart Rate Intensity and Skill Development.

ERIC Educational Resources Information Center

Quinn, Patrick B.; Strand, Brad

1995-01-01

This study examined the effect of adding aerobic training to football skills development activities for male seventh graders. Two groups completed one or the other type of training. Heart rate monitor and skill assessment data indicated that the addition of the planned fitness component did not detract from skill development. (SM)

Impact of Pubertal Development and Physical Activity on Heart Rate Variability in Overweight and Obese Children in Taiwan

ERIC Educational Resources Information Center

Chen, Su-Ru; Chiu, Hung-Wen; Lee, Yann-Jinn; Sheen, Tzong-Chi; Jeng, Chii

2012-01-01

Child obesity is frequently associated with dysfunction of autonomic nervous system. Children in pubertal development were suggested to be vulnerable to autonomic nervous system problems such as decrease of heart rate variability from dysregulation of metabolic control. This study explored the influence of pubertal development on autonomic nervous…

Histone methylations in heart development, congenital and adult heart diseases.

PubMed

Zhang, Qing-Jun; Liu, Zhi-Ping

2015-01-01

Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases.

Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart

PubMed Central

Cardona, Maria; López, Juan Antonio; Serafín, Anna; Rongvaux, Anthony; Inserte, Javier; García-Dorado, David; Flavell, Richard; Llovera, Marta; Cañas, Xavier; Vázquez, Jesús; Sanchis, Daniel

2015-01-01

Executioner caspase-3 and -7 are proteases promoting cell death but non-apoptotic roles are being discovered. The heart expresses caspases only during development, suggesting they contribute to the organ maturation process. Therefore, we aimed at identifying novel functions of caspases in heart development. We induced simultaneous deletion of executioner caspase-3 and -7 in the mouse myocardium and studied its effects. Caspase knockout hearts are hypoplastic at birth, reaching normal weight progressively through myocyte hypertrophy. To identify the molecular pathways involved in these effects, we used microarray-based transcriptomics and multiplexed quantitative proteomics to compare wild type and executioner caspase-deficient myocardium at different developmental stages. Transcriptomics showed reduced expression of genes promoting DNA replication and cell cycle progression in the neonatal caspase-deficient heart suggesting reduced myocyte proliferation, and expression of non-cardiac isoforms of structural proteins in the adult null myocardium. Proteomics showed reduced abundance of proteins involved in oxidative phosphorylation accompanied by increased abundance of glycolytic enzymes underscoring retarded metabolic maturation of the caspase-null myocardium. Correlation between mRNA expression and protein abundance of relevant genes was confirmed, but transcriptomics and proteomics indentified complementary molecular pathways influenced by caspases in the developing heart. Forced expression of wild type or proteolytically inactive caspases in cultured cardiomyocytes induced expression of genes promoting cell division. The results reveal that executioner caspases can modulate heart’s cellularity and maturation during development, contributing novel information about caspase biology and heart development. PMID:26121671

Biomechanics of Cardiac Function

PubMed Central

Voorhees, Andrew P.; Han, Hai-Chao

2015-01-01

The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

Needs of caregivers in heart failure management: A qualitative study

PubMed Central

Frost, Julia; Britten, Nicky; Jolly, Kate; Greaves, Colin; Abraham, Charles; Dalal, Hayes

2015-01-01

Objectives To identify the needs of caregivers supporting a person with heart failure and to inform the development of a caregiver resource to be used as part of a home-based self-management programme. Methods A qualitative study informed by thematic analysis involving 26 caregivers in individual interviews or a focus group. Results Three distinct aspects of caregiver support in heart failure management were identified. Firstly, caregivers identified needs about supporting management of heart failure including: coping with the variability of heart failure symptoms, what to do in an emergency, understanding and managing medicines, providing emotional support, promoting exercise and physical activity, providing personal care, living with a cardiac device and supporting depression management. Secondly, as they make the transition to becoming a caregiver, they need to develop skills to undertake difficult discussions about the role; communicate with health professionals; manage their own mental health, well-being and sleep; and manage home and work. Thirdly, caregivers require skills to engage social support, and voluntary and formal services while recognising that the long-term future is uncertain. Discussion The identification of the needs of caregiver has been used to inform the development of a home-based heart failure intervention facilitated by a trained health care practitioner. PMID:25795144

Heart-specific expression of laminopathic mutations in transgenic zebrafish.

PubMed

Verma, Ajay D; Parnaik, Veena K

2017-07-01

Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development. © 2017 International Federation for Cell Biology.

Lack of genetic interaction between Tbx20 and Tbx3 in early mouse heart development.

PubMed

Gavrilov, Svetlana; Harvey, Richard P; Papaioannou, Virginia E

2013-01-01

Members of the T-box family of transcription factors are important regulators orchestrating the complex regionalization of the developing mammalian heart. Individual mutations in Tbx20 and Tbx3 cause distinct congenital heart abnormalities in the mouse: Tbx20 mutations result in failure of heart looping, developmental arrest and lack of chamber differentiation, while hearts of Tbx3 mutants progress further, loop normally but show atrioventricular convergence and outflow tract defects. The two genes have overlapping areas of expression in the atrioventricular canal and outflow tract of the heart but their potential genetic interaction has not been previously investigated. In this study we produced compound mutants to investigate potential genetic interactions at the earliest stages of heart development. We find that Tbx20; Tbx3 double heterozygous mice are viable and fertile with no apparent abnormalities, while double homozygous mutants are embryonic lethal by midgestation. Double homozygous mutant embryos display abnormal cardiac morphogenesis, lack of heart looping, expression patterns of cardiac genes and time of death that are indistinguishable from Tbx20 homozygous mutants. Prior to death, the double homozygotes show an overall developmental delay similar to Tbx3 homozygous mutants. Thus the effects of Tbx20 are epistatic to Tbx3 in the heart but Tbx3 is epistatic to Tbx20 with respect to developmental delay.

Long-Term Follow-Up of Children with Heart Block Born from Mothers with Systemic Lupus Erythematosus: A Retrospective Study from the Database Pediatric and Congenital Heart Disease in University Hospitals Leuven.

PubMed

DE Caluwé, Eva; VAN DE Bruaene, Alexander; Willems, Rik; Troost, Els; Gewillig, Marc; Rega, Filip; Budts, Werner

2016-09-01

Children from mothers with systemic lupus erythematosus are frequently born with congenital heart block. This study aimed at evaluating long-term outcome because long-term data are scarce. In the database of pediatric and congenital heart disease (University Hospitals Leuven), 19 children from systemic lupus erythematosus mothers and who were born with or developed atrioventricular block were identified. All records were reviewed for disease course and outcome. Median follow-up time was 7 years (interquartile ranges [IQR] 4.5-13 years). One child had no heart block at birth and developed only a first-degree block during follow-up. One had a second-degree heart block and developed a complete heart block. Seventeen patients (89%) were born with a complete heart block. Seventeen patients (89%) needed a definitive pacemaker. In all, epicardial leads were used at first implantation. Eighty-two percent received their pacemaker in the first year of life. The first battery had a median lifetime of 5 years (IQR 3.5-5 years), the second 6 years (IQR 4.5-6.3 years), and the third 5 years (IQR 5-6 years). Note that 47% of patients needed a lead replacement due to lead problems. Only one pericardial tamponade after pacemaker implantation. No device or lead infections occurred. The left ventricular systolic function at latest follow-up was normal for all. No patients died. In children with heart block born from systemic lupus erythematosus mothers, an early need for pacemaker implantation was documented. The overall battery life was acceptable, but there was a high need for lead replacement. Complication rate was low. Late outcome was good. © 2016 Wiley Periodicals, Inc.

Diabetic Cardiomyopathy and Metabolic Remodeling of the Heart

PubMed Central

Battiprolu, Pavan K.; Lopez-Crisosto, Camila; Wang, Zhao V.; Nemchenko, Andriy; Lavandero, Sergio; Hill, Joseph A.

2012-01-01

The incidence and prevalence of diabetes mellitus are each increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential. PMID:23123443

Cardiac telomere length in heart development, function, and disease.

PubMed

Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

Effect of uterine contractions on fetal heart rate in pregnancy: a prospective observational study.

PubMed

Sletten, Julie; Kiserud, Torvid; Kessler, Jörg

2016-10-01

The new Holter monitoring technology enables long-term electrocardiographic recording of the fetal heart rate without discomfort for the mother. The aim of the study was to assess the feasibility of a fetal Holter monitor. This technology was further used to study fetal heart rate outside the hospital setting during normal daily activities and to test the hypothesis that uterine activity during pregnancy influences fetal heart rate. Prospective observational study including 12 healthy pregnant women at 20-40 weeks of gestation. Data were collected using the Monica AN24 system. Outcome measures were fetal heart rate, maternal heart rate, and uterine activity categorized according to the strength of the electrohysterographic signal. The recordings had a median length of 18.8 h, and fetal heart rate and maternal heart rate were obtained with success rates of 73.1 and 99.9%, respectively. Uterine activity was found to affect fetal heart rate in all participants. Compared with the basal tone and mild levels of uterine activity, moderate and strong levels of uterine activity were associated with increases in fetal heart rate of 4.0 and 5.7 beats/min, respectively. At night, the corresponding increases were 4.9 and 7.6 beats/min. Linear correlations were found between maternal heart rate and fetal heart rate in 11 of the 12 cases, with a mean coefficient beta of 0.189. Both maternal heart rate and fetal heart rate exhibited a diurnal pattern, with lower heart rates being recorded at night. Uterine activity during pregnancy is associated with a graded response in fetal heart rate and may represent a physiological challenge for the development and adaptation of the fetal cardiovascular system. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Long‐term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study

PubMed Central

Ho, Jennifer E.; Larson, Martin G.; Ghorbani, Anahita; Cheng, Susan; Coglianese, Erin E.; Vasan, Ramachandran S.; Wang, Thomas J.

2014-01-01

Background Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow‐up. Methods and Results Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all‐cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001). Conclusions Individuals with a higher heart rate are at elevated long‐term risk for cardiovascular events, in particular, heart failure, and all‐cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation. PMID:24811610

The risk of falling into poverty after developing heart disease: a survival analysis.

PubMed

Callander, Emily J; Schofield, Deborah J

2016-07-15

Those with a low income are known to have a higher risk of developing heart disease. However, the inverse relationship - falling into income poverty after developing heart disease has not been explored with longitudinal data. This paper aims to determine if those with heart disease have an elevated risk of falling into poverty. Survival analysis was conducted using the longitudinal Household Income and Labour Dynamics in Australia survey, between the years 2007 and 2012. The study focused on the Australian population aged 21 years and over in 2007 who were not already in poverty and did not already have heart disease, who were followed from 2007 to 2012. Cox regression models adjusting for age, sex and time-varying co-variates (marital status, home ownership and remoteness of area of residence) were constructed to assess the risk of falling into poverty. For those aged 20 who developed heart disease, the hazard ratio for falling into income poverty was 9.24 (95 % CI: 8.97-9.51) and for falling into multidimensional poverty the hazard ratio was 14.21 (95 % CI: 13.76-14.68); for those aged 40 the hazard ratio for falling into income poverty was 3.45 (95 % CI: 3.39-3.51) and for multidimensional poverty, 5.20 (95 % CI: 5.11-5.29); and for those aged 60 the hazard ratio for falling into income poverty was 1.29 (95 % CI: 1.28-1.30) and for multidimensional poverty, 1.52 (95 % CI: 1.51-1.54), relative those who never developed heart disease. The risk for both income and multidimensional poverty decreases with age up to the age of 70, over which, those who developed heart disease had a reduced risk of poverty. For those under the age of 70, developing heart disease is associated with an increased risk of falling into both income poverty and multidimensional poverty.

Influence of energy drinks and alcohol on post-exercise heart rate recovery and heart rate variability.

PubMed

Wiklund, Urban; Karlsson, Marcus; Oström, Mats; Messner, Torbjörn

2009-01-01

Media have anecdotally reported that drinking energy drinks in combination with alcohol and exercise could cause sudden cardiac death. This study investigated changes in the electrocardiogram (ECG) and heart rate variability after intake of an energy drink, taken in combination with alcohol and exercise. Ten healthy volunteers (five men and five women aged 19-30) performed maximal bicycle ergometer exercise for 30 min after: (i) intake of 0.75 l of an energy drink mixed with alcohol; (ii) intake of energy drink; and, (iii) no intake of any drink. ECG was continuously recorded for analysis of heart rate variability and heart rate recovery. No subject developed any clinically significant arrhythmias. Post-exercise recovery in heart rate and heart rate variability was slower after the subjects consumed energy drink and alcohol before exercise, than after exercise alone. The healthy subjects developed blunted cardiac autonomic modulation after exercising when they had consumed energy drinks mixed with alcohol. Although they did not develop any significant arrhythmia, individuals predisposed to arrhythmia by congenital or other rhythm disorders could have an increased risk for malignant cardiac arrhythmia in similar situations.

Does fractality in heart rate variability indicate the development of fetal neural processes?

NASA Astrophysics Data System (ADS)

Echeverría, J. C.; Woolfson, M. S.; Crowe, J. A.; Hayes-Gill, B. R.; Piéri, Jean F.; Spencer, C. J.; James, D. K.

2004-10-01

By using an improved detrended fluctuation analysis we studied the scaling behaviour of 53 long-term series of fetal heart rate fluctuations. Our results suggest that fractality begins to arise around 24 weeks of normal human gestation and that this condition, showing some additional developments, seems to be preserved during gestation. This may provide new evidence of a role played by cortical-to-subcortical pathways in the long-term fractal nature of heart rate variability data.

The Feasibility of Using the BrightHearts Biofeedback-Assisted Relaxation Application for the Management of Pediatric Procedural Pain: A Pilot Study.

PubMed

Burton, Karen L O; Morrow, Angela M; Beswick, Brooke V; Khut, George P

2018-04-17

The objective of this pilot study was to assess the acceptability and feasibility of using BrightHearts, a biofeedback-assisted relaxation application (app), in children undergoing painful procedures. Thirty children 7 to 18 years of age undergoing a medical procedure (peripheral blood collection, botulinum toxin injection, or intravenous cannula insertion) participated. Participants used BrightHearts, a heart rate-controlled biofeedback-assisted relaxation training app delivered via an iPad with heart rate measured through a pulse oximeter worn on the ear or thumb. Feasibility was assessed through observations and patient, parent/carer, and healthcare professional feedback. Patient, parent/carer, and healthcare professional satisfaction with BrightHearts was rated using investigator-developed surveys. Eighty-three percent of child participants reported that they found BrightHearts helpful during the procedure and that they would use BrightHearts again. All parents and 96% of healthcare professionals indicated they would use BrightHearts again. Sixty-four percent of healthcare providers perceived that BrightHearts assisted with the ease of performing the procedure. Qualitative analyses found 2 themes: (1) BrightHearts calms through providing distraction and biofeedback and (2) the impact of BrightHearts on the procedure. This pilot study demonstrates the feasibility of using biofeedback-assisted relaxation delivered via the BrightHearts app in children undergoing peripheral blood collection and cannulation. Future studies are required to evaluate BrightHearts' efficacy in reducing pain and anxiety during painful procedures and distinguish the effects of a biofeedback-mediated app from distraction. © 2018 World Institute of Pain.

Measurement of wall shear stress in chick embryonic heart using optical coherence tomography

NASA Astrophysics Data System (ADS)

Ma, Zhenhe; Dou, Shidan; Zhao, Yuqian; Wang, Yi; Suo, Yanyan; Wang, Fengwen

2015-03-01

The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) is one of the components which have been proved to influence the morphogenesis during early stages of cardiac development. To study the mechanism, WSS measurement is a step with significant importance. WSS is caused by blood flow imposed on the inner surface of the heart wall and it can be determined by calculating velocity gradients of blood flow in a direction perpendicular to the wall. However, the WSS of the early stage embryonic heart is difficult to measure since the embryonic heart is tiny and beating fast. Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial and temporal resolution, which is uniquely suitable for the study of early stage embryonic heart development. In this paper, we introduce a method to measure the WSS of early stage chick embryonic heart based on high speed spectral domain optical coherence tomography (SDOCT). 4D (x,y,z,t) scan was performed on the outflow tract (OFT) of HH18 (~3 days of incubation) chick embryonic heart. After phase synchronization, OFT boundary segmentation, and OFT center line calculation, Doppler angle of the blood flow in the OFT can be achieved (This method has been described in previous publications). Combining with the Doppler OCT results, we calculate absolute blood flow velocity distribution in the OFT. The boundary of the OFT was segmented at each cross-sectional structural image, then geometrical center of the OFT can be calculated. Thus, the gradients of blood flow in radial direction can be calculated. This velocity gradient near the wall is termed wall shear rate and the WSS value is proportional to the wall shear rate. Based on this method, the WSS at different heart beating phase are compare. The result demonstrates that OCT is capable of early stage chicken embryonic heart WSS study.

Resting heart rate and the risk of developing impaired fasting glucose and diabetes: the Kailuan prospective study

PubMed Central

Wang, Liang; Cui, Liufu; Wang, Yanxue; Vaidya, Anand; Chen, Shuohua; Zhang, Caifeng; Zhu, Ying; Li, Dongqing; Hu, Frank B; Wu, Shouling; Gao, Xiang

2015-01-01

Background: To investigate the association between resting heart rate and the risk of developing impaired fasting glucose (IFG), diabetes and conversion from IFG to diabetes. Methods: The prospective analysis included 73 357 participants of the Kailuan cohort (57 719 men and 15 638 women). Resting heart rate was measured via electrocardiogram in 2006. Incident diabetes was defined as either the fasting blood glucose (FBG) ≥ 7.0 mmol/l or new active use of diabetes medications during the 4-year follow-up period. IFG was defined as a FBG between 5.6 and 6.9 mmol/l. A meta-analysis including seven published prospective studies focused on heart rate and diabetes risk, and our current study was then conducted using random-effects models. Results: During 4 years of follow-up, 17 463 incident IFG cases and 4 649 incident diabetes cases were identified. The corresponding adjusted hazard ratios (HRs) for each 10 beats/min increase in heart rate were 1.23 [95% confidence interval (CI): 1.19, 1.27] for incident diabetes, 1.11 (95% CI: 1.09, 1.13) for incident IFG and 1.13 (95% CI: 1.08, 1.17) for IFG to diabetes conversion. The risks of incident IFG and diabetes were significantly higher among participants aged < 50 years than those aged ≥ 50 years (P-interaction < 0.02 for both). A meta-analysis confirmed the positive association between resting heart rate and diabetes risk (pooled HR for the highest vs lowest heart rate quintile = 1.59, 95% CI:1.27, 2.00; n = 8). Conclusion: Faster resting heart rate is associated with higher risk of developing IFG and diabetes, suggesting that heart rate could be used to identify individuals with a higher future risk of diabetes. PMID:26002923

Next-generation models of human cardiogenesis via genome editing.

PubMed

Lian, Xiaojun; Xu, Jiejia; Li, Jinsong; Chien, Kenneth R

2014-09-18

Cardiogenesis is one of the earliest and most important steps during human development and is orchestrated by discrete families of heart progenitors, which build distinct regions of the fetal heart. For the past decade, a lineage map for the distinct subsets of progenitors that generate the embryonic mammalian heart has begun to lay a foundation for the development of new strategies for rebuilding the adult heart after injury, an unmet clinical need for the vast majority of patients with end-stage heart failure who are not heart transplant recipients. The studies also have implications for the root causes of congenital heart disease, which affects 1 in 50 live births, the most prevalent malformations in children. Although much of this insight has been generated in murine models, it is becoming increasingly clear that there can be important divergence with principles and pathways for human cardiogenesis, as well as for regenerative pathways. The development of human stem cell models, coupled with recent advances in genome editing with RNA-guided endonucleases, offers a new approach for the primary study of human cardiogenesis. In addition, application of the technology to the in vivo setting in large animal models, including nonhuman primates, has opened the door to genome-edited large animal models of adult and congenital heart disease, as well as a detailed mechanistic dissection of the more diverse and complex set of progenitor families and pathways, which guide human cardiogenesis. Implications of this new technology for a new generation of human-based, genetically tractable systems are discussed, along with potential therapeutic applications. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications

PubMed Central

Gay, Maresha S.; Li, Yong; Xiong, Fuxia; Lin, Thant; Zhang, Lubo

2015-01-01

The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner. PMID:25923220

Cardiac Gab1 deletion leads to dilated cardiomyopathy associated with mitochondrial damage and cardiomyocyte apoptosis

PubMed Central

Zhao, J; Yin, M; Deng, H; Jin, F Q; Xu, S; Lu, Y; Mastrangelo, M A; Luo, H; Jin, Z G

2016-01-01

A vital step in the development of heart failure is the transition from compensatory cardiac hypertrophy to decompensated dilated cardiomyopathy (DCM) during cardiac remodeling under mechanical or pathological stress. However, the molecular mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we investigate whether Gab1, a scaffolding adaptor protein, protects against hemodynamic stress-induced DCM and heat failure. We first observed that the protein levels of Gab1 were markedly reduced in hearts from human patients with DCM and from mice with experimental viral myocarditis in which DCM developed. Next, we generated cardiac-specific Gab1 knockout mice (Gab1-cKO) and found that Gab-cKO mice developed DCM in hemodynamic stress-dependent and age-dependent manners. Under transverse aorta constriction (TAC), Gab1-cKO mice rapidly developed decompensated DCM and heart failure, whereas Gab1 wild-type littermates exhibited adaptive left ventricular hypertrophy without changes in cardiac function. Mechanistically, we showed that Gab1-cKO mouse hearts displayed severe mitochondrial damages and increased cardiomyocyte apoptosis. Loss of cardiac Gab1 in mice impaired Gab1 downstream MAPK signaling pathways in the heart under TAC. Gene profiles further revealed that ablation of Gab1 in heart disrupts the balance of anti- and pro-apoptotic genes in cardiomyocytes. These results demonstrate that cardiomyocyte Gab1 is a critical regulator of the compensatory cardiac response to aging and hemodynamic stress. These findings may provide new mechanistic insights and potential therapeutic target for DCM and heart failure. PMID:26517531

Genome-wide compendium and functional assessment of in vivo heart enhancers

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

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

DOE PAGES

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; ...

2016-10-05

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of > 35 epigenomic data sets from mouse and human pre-and postnatal hearts we created a comprehensive reference of > 80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs ofmore » two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function.« less

Genome-wide compendium and functional assessment of in vivo heart enhancers

PubMed Central

Dickel, Diane E.; Barozzi, Iros; Zhu, Yiwen; Fukuda-Yuzawa, Yoko; Osterwalder, Marco; Mannion, Brandon J.; May, Dalit; Spurrell, Cailyn H.; Plajzer-Frick, Ingrid; Pickle, Catherine S.; Lee, Elizabeth; Garvin, Tyler H.; Kato, Momoe; Akiyama, Jennifer A.; Afzal, Veena; Lee, Ah Young; Gorkin, David U.; Ren, Bing; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2016-01-01

Whole-genome sequencing is identifying growing numbers of non-coding variants in human disease studies, but the lack of accurate functional annotations prevents their interpretation. We describe the genome-wide landscape of distant-acting enhancers active in the developing and adult human heart, an organ whose impairment is a predominant cause of mortality and morbidity. Using integrative analysis of >35 epigenomic data sets from mouse and human pre- and postnatal hearts we created a comprehensive reference of >80,000 putative human heart enhancers. To illustrate the importance of enhancers in the regulation of genes involved in heart disease, we deleted the mouse orthologs of two human enhancers near cardiac myosin genes. In both cases, we observe in vivo expression changes and cardiac phenotypes consistent with human heart disease. Our study provides a comprehensive catalogue of human heart enhancers for use in clinical whole-genome sequencing studies and highlights the importance of enhancers for cardiac function. PMID:27703156

The effect of competition on heart rate during kart driving: A field study.

PubMed

Matsumura, Kenta; Yamakoshi, Takehiro; Yamakoshi, Yasuhiro; Rolfe, Peter

2011-09-09

Both the act of competing, which can create a kind of mental stress, and participation in motor sports, which induces physical stress from intense g-forces, are known to increase heart rate dramatically. However, little is known about the specific effect of competition on heart rate during motor sports, particularly during four-wheel car driving. The goal of this preliminary study, therefore, was to investigate whether competition increases heart rate under such situations. The participants drove an entry-level formula kart during two competitive races and during solo driving against the clock while heart rate and g-forces were measured. Analyses showed that heart rate values during the races (168.8 beats/min) were significantly higher than those during solo driving (140.9 beats/min) and rest (75.1 beats/min). The results of this preliminary study indicate that competition heightens heart rate during four-wheel car driving. Kart drivers should be concerned about maintaining good health and developing physical strength.

The effect of competition on heart rate during kart driving: A field study

PubMed Central

2011-01-01

Background Both the act of competing, which can create a kind of mental stress, and participation in motor sports, which induces physical stress from intense g-forces, are known to increase heart rate dramatically. However, little is known about the specific effect of competition on heart rate during motor sports, particularly during four-wheel car driving. The goal of this preliminary study, therefore, was to investigate whether competition increases heart rate under such situations. Findings The participants drove an entry-level formula kart during two competitive races and during solo driving against the clock while heart rate and g-forces were measured. Analyses showed that heart rate values during the races (168.8 beats/min) were significantly higher than those during solo driving (140.9 beats/min) and rest (75.1 beats/min). Conclusions The results of this preliminary study indicate that competition heightens heart rate during four-wheel car driving. Kart drivers should be concerned about maintaining good health and developing physical strength. PMID:21906298

Qualitative research of alternatively splice variants of fibronectin in different development stage of mice heart.

PubMed

Lu, Feng; Ma, Fang-Fang; Zhang, Wei; Li, Ying; Wei, Fei-Yu; Zhou, Lei

2015-12-01

Fibronectin (FN) plays vital roles in cell adhesion, differentiation, proliferation and migration. It is involved in the process of embryonic development and is highly conserved during evolution. The EIIIA and EIIIB of FN show a very high degree of homology among vertebrates. Embryos deleting both EIIIA and EIIIB displayed multiple embryonic cardiovascular defects, implying their crucial role during embryogenesis. The correlation of spliced EIIIB, EIIIA, and IIICS of FN to heart development was studied by observing their chronological expression in mice heart. C57 mice embryos at E11.5, E12.5, E13.5, E14.5, E15.5, E16.5, E17.5, E18.5, E19.5 days, postnatal day 1 (P1d), and adult male mice (3 months) were used. For each alternatively spliced FN1 domain (EIIIB, EIIIA and IIICS), primer pairs were designed for specific amplification. Total RNA was extracted from the heart tissue, reverse transcripted to cDNA, followed by RT-PCR with specific primers. The PCR amplification was verified by agarose gel electrophoresis, showing specific fragments of the expected sizes. In adult mice heart, only alternatively splice variants of EIIIA-, EIIIB-, IIICS+ were expressed. While in embryonic mice, spliced variant of EIIIA+/-, EIIIB+/-, IIICS+ were observed. The expression of EIIIA and EIIIB changed during heart development. FN is crucial for the normal development of the embryonic heart by modulating cardiac neural crest (CNC) proliferation and survival, and maintenance of CNC cells. FN1 gene seems to play a significant role by expression of highly conserved EIIIA and EIIIB in embryonic heart development.

A protocol to study ex vivo mouse working heart at human-like heart rate.

PubMed

Feng, Han-Zhong; Jin, Jian-Ping

2018-01-01

Genetically modified mice are widely used as experimental models to study human heart function and diseases. However, the fast rate of normal mouse heart at 400-600bpm limits its capacity of assessing kinetic parameters that are important for the physiology and pathophysiology of human heart that beats at a much slower rate (75-180bpm). To extend the value of mouse models, we established a protocol to study ex vivo mouse working hearts at a human-like heart rate. In the presence of 300μM lidocaine to lower pacemaker and conductive activities and prevent arrhythmia, a stable rate of 120-130bpm at 37°C is achieved for ex vivo mouse working hearts. The negative effects of decreased heart rate on force-frequency dependence and lidocaine as a myocardial depressant on intracellular calcium can be compensated by using a higher but still physiological level of calcium (2.75mM) in the perfusion media. Multiple parameters were studied to compare the function at the human-like heart rate with that of ex vivo mouse working hearts at the standard rate of 480bpm. The results showed that the conditions for slower heart rate in the presence of 300μM lidocaine did not have depressing effect on left ventricular pressure development, systolic and diastolic velocities and stroke volume with maintained positive inotropic and lusitropic responses to β-adrenergic stimulation. Compared with that at 480bpm, the human-like heart rate increased ventricular filling and end diastolic volume with enhanced Frank-Starling responses. Coronary perfusion was increased from longer relaxation time and interval between beats whereas cardiac efficiency was significantly improved. Although the intrinsic differences between mouse and human heart remain, this methodology for ex vivo mouse hearts to work at human-like heart rate extends the value of using genetically modified mouse models to study cardiac function and human heart diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in gravitational force induce alterations in gene expression that can be monitored in the live, developing zebrafish heart

NASA Astrophysics Data System (ADS)

Gillette-Ferguson, I.; Ferguson, D. G.; Poss, K. D.; Moorman, S. J.

2003-10-01

Little is known about the effect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a β-actin promoter, we examined the affect of simulated-microgravity on GFP expression in the heart. Zebrafish embryos, at the 18-20 somite-stage, were exposed to simulated-microgravity for 24 hours. The intensity of GFP fluorescence associated with the heart was then determined using fluorescence microscopy. Our measurements indicated that simulated-microgravity induced a 23.9% increase in GFP-associated fluorescence in the heart. In contrast, the caudal notochord showed a 17.5% increase and the embryo as a whole showed only an 8.5% increase in GFP-associated fluorescence. This suggests that there are specific effects on the heart causing the more dramatic increase. These studies indicate that microgravity can influence gene expression and demonstrate the usefulness of this in vivo model of "reporter-gene" expression for studying the effects of microgravity.

Factors Related to Self-Care in Heart Failure Patients According to the Middle-Range Theory of Self-Care of Chronic Illness: a Literature Update.

PubMed

Jaarsma, Tiny; Cameron, Jan; Riegel, Barbara; Stromberg, Anna

2017-04-01

As described in the theory of self-care in chronic illness, there is a wide range of factors that can influence self-care behavior. The purpose of this paper is to summarize the recent heart failure literature on these related factors in order to provide an overview on which factors might be suitable to be considered to make self-care interventions more successful. Recent studies in heart failure patients confirm that factors described in the theory of self-care of chronic illness are relevant for heart failure patients. Experiences and skills, motivation, habits, cultural beliefs and values, functional and cognitive abilities, confidence, and support and access to care are all important to consider when developing or improving interventions for patients with heart failure and their families. Additional personal and contextual factors that might influence self-care need to be explored and included in future studies and theory development efforts.

Automatic Emboli Detection System for the Artificial Heart

NASA Astrophysics Data System (ADS)

Steifer, T.; Lewandowski, M.; Karwat, P.; Gawlikowski, M.

In spite of the progress in material engineering and ventricular assist devices construction, thromboembolism remains the most crucial problem in mechanical heart supporting systems. Therefore, the ability to monitor the patient's blood for clot formation should be considered an important factor in development of heart supporting systems. The well-known methods for automatic embolus detection are based on the monitoring of the ultrasound Doppler signal. A working system utilizing ultrasound Doppler is being developed for the purpose of flow estimation and emboli detection in the clinical artificial heart ReligaHeart EXT. Thesystem will be based on the existing dual channel multi-gate Doppler device with RF digital processing. A specially developed clamp-on cannula probe, equipped with 2 - 4 MHz piezoceramic transducers, enables easy system setup. We present the issuesrelated to the development of automatic emboli detection via Doppler measurements. We consider several algorithms for the flow estimation and emboli detection. We discuss their efficiency and confront them with the requirements of our experimental setup. Theoretical considerations are then met with preliminary experimental findings from a) flow studies with blood mimicking fluid and b) in-vitro flow studies with animal blood. Finally, we discuss some more methodological issues - we consider several possible approaches to the problem of verification of the accuracy of the detection system.

Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC (Chronic Renal Insufficiency Cohort) Study.

PubMed

He, Jiang; Shlipak, Michael; Anderson, Amanda; Roy, Jason A; Feldman, Harold I; Kallem, Radhakrishna Reddy; Kanthety, Radhika; Kusek, John W; Ojo, Akinlolu; Rahman, Mahboob; Ricardo, Ana C; Soliman, Elsayed Z; Wolf, Myles; Zhang, Xiaoming; Raj, Dominic; Hamm, Lee

2017-05-17

Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24-hour urine albumin excretion. During an average of 6.3 years of follow-up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine-based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C-based-eGFR was 2.43 (2.10, 2.80), and 1 SD higher log-albuminuria was 1.65 (1.53, 1.78), all P <0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C-based eGFR and higher log-albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P =0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P =0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P <0.001), interleukin-6 (1.15, 95% CI 1.05, 1.25, P =0.002), and tumor necrosis factor-α (1.10, 95% CI 1.00, 1.21, P =0.05) were all significantly and directly associated with incidence of heart failure. Our study indicates that cystatin C-based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine-based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Genetics of Congenital Heart Disease: Past and Present.

PubMed

Muntean, Iolanda; Togănel, Rodica; Benedek, Theodora

2017-04-01

Congenital heart disease is the most common congenital anomaly, representing an important cause of infant morbidity and mortality. Congenital heart disease represents a group of heart anomalies that include septal defects, valve defects, and outflow tract anomalies. The exact genetic, epigenetic, or environmental basis of congenital heart disease remains poorly understood, although the exact mechanism is likely multifactorial. However, the development of new technologies including copy number variants, single-nucleotide polymorphism, next-generation sequencing are accelerating the detection of genetic causes of heart anomalies. Recent studies suggest a role of small non-coding RNAs, micro RNA, in congenital heart disease. The recently described epigenetic factors have also been found to contribute to cardiac morphogenesis. In this review, we present past and recent genetic discoveries in congenital heart disease.

Analysis of cardiomyocyte movement in the developing murine heart

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

Hashimoto, Hisayuki; Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp; Tabata, Hidenori

The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cellmore » cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.« less

The Representation of Heart Development in the Gene Ontology

PubMed Central

Khodiyar, Varsha K.; Hill, David P.; Howe, Doug; Berardini, Tanya Z.; Tweedie, Susan; Talmud, Philippa J.; Breckenridge, Ross; Bhattarcharya, Shoumo; Riley, Paul; Scambler, Peter; Lovering, Ruth C.

2012-01-01

An understanding of heart development is critical in any systems biology approach to cardiovascular disease. The interpretation of data generated from high-throughput technologies (such as microarray and proteomics) is also essential to this approach. However, characterizing the role of genes in the processes underlying heart development and cardiovascular disease involves the non-trivial task of data analysis and integration of previous knowledge. The Gene Ontology (GO) Consortium provides structured controlled biological vocabularies that are used to summarize previous functional knowledge for gene products across all species. One aspect of GO describes biological processes, such as development and signaling. In order to support high-throughput cardiovascular research, we have initiated an effort to fully describe heart development in GO; expanding the number of GO terms describing heart development from 12 to over 280. This new ontology describes heart morphogenesis, the differentiation of specific cardiac cell types, and the involvement of signaling pathways in heart development and aligns GO with the current views of the heart development research community and its representation in the literature. This extension of GO allows gene product annotators to comprehensively capture the genetic program leading to the developmental progression of the heart. This will enable users to integrate heart development data across species, resulting in the comprehensive retrieval of information about this subject. The revised GO structure, combined with gene product annotations, should improve the interpretation of data from high-throughput methods in a variety of cardiovascular research areas, including heart development, congenital cardiac disease, and cardiac stem cell research. Additionally, we invite the heart development community to contribute to the expansion of this important dataset for the benefit of future research in this area. PMID:21419760

Machine learning in heart failure: ready for prime time.

PubMed

Awan, Saqib Ejaz; Sohel, Ferdous; Sanfilippo, Frank Mario; Bennamoun, Mohammed; Dwivedi, Girish

2018-03-01

The aim of this review is to present an up-to-date overview of the application of machine learning methods in heart failure including diagnosis, classification, readmissions and medication adherence. Recent studies have shown that the application of machine learning techniques may have the potential to improve heart failure outcomes and management, including cost savings by improving existing diagnostic and treatment support systems. Recently developed deep learning methods are expected to yield even better performance than traditional machine learning techniques in performing complex tasks by learning the intricate patterns hidden in big medical data. The review summarizes the recent developments in the application of machine and deep learning methods in heart failure management.

Morphology and biomechanics of human heart

NASA Astrophysics Data System (ADS)

Chelnokova, Natalia O.; Golyadkina, Anastasiya A.; Kirillova, Irina V.; Polienko, Asel V.; Ivanov, Dmitry V.

2016-03-01

Object of study: A study of the biomechanical characteristics of the human heart ventricles was performed. 80 hearts were extracted during autopsy of 80 corpses of adults (40 women and 40 men) aged 31-70 years. The samples were investigated in compliance with the recommendations of the ethics committee. Methods: Tension and compression tests were performed with help of the uniaxial testing machine Instron 5944. Cardiometry was also performed. Results: In this work, techniques for human heart ventricle wall biomechanical properties estimation were developed. Regularities of age and gender variability in deformative and strength properties of the right and left ventricle walls were found. These properties were characterized by a smooth growth of myocardial tissue stiffness and resistivity at a relatively low strain against reduction in their strength and elasticity from 31-40 to 61-70 years. It was found that tissue of the left ventricle at 61-70 years had a lower stretchability and strength compared with tissues of the right ventricle and septum. These data expands understanding of the morphological organization of the heart ventricles, which is very important for the development of personalized medicine. Taking into account individual, age and gender differences of the heart ventricle tissue biomechanical characteristics allows to rationally choosing the type of patching materials during reconstructive operations on heart.

Broken heart: depression in cardiovascular disease

PubMed Central

Krishnan, K. Ranga R.

2003-01-01

Heart disease and depression are among the most common diseases seen in developed countries. The relation-ship between heart disease and depression has been the subject of both popular interest and scientific research. Sadness is often portrayed as a feeling of heaviness in the chest or as a “broken heart.” Interestingly as we learn more about the expression of emotions, it appears that these perceptions may simply be the language representation of somatic feelings. Large, prospective, longitudinal studies that have examined the relationship between depression and development of coronary artery disease (CAD) have shown that depression is a risk factor for the development of CAD. Depression also increases mortality in patients with stable CAD or myocardial infarction compared with patients without depression. The recent Sertraline AntiDepressant HeARt attack Trial (SADHART) has shown that selective serotonin reuptake inhibitors like sertraline can be safely used in patients with depression following myocardial infarction. There is also intriguing evidence that treating depression with antidepressants may improve outcomes, including mortality. PMID:22034195

Development and psychometric evaluation of the Thirst Distress Scale for patients with heart failure.

PubMed

Waldréus, Nana; Jaarsma, Tiny; van der Wal, Martje Hl; Kato, Naoko P

2018-03-01

Patients with heart failure can experience thirst distress. However, there is no instrument to measure this in patients with heart failure. The aim of the present study was to develop the Thirst Distress Scale for patients with Heart Failure (TDS-HF) and to evaluate psychometric properties of the scale. The TDS-HF was developed to measure thirst distress in patients with heart failure. Face and content validity was confirmed using expert panels including patients and healthcare professionals. Data on the TDS-HF was collected from patients with heart failure at outpatient heart failure clinics and hospitals in Sweden, the Netherlands and Japan. Psychometric properties were evaluated using data from 256 heart failure patients (age 72±11 years). Concurrent validity of the scale was assessed using a thirst intensity visual analogue scale. Patients did not have any difficulties answering the questions, and time taken to answer the questions was about five minutes. Factor analysis of the scale showed one factor. After psychometric testing, one item was deleted. For the eight item TDS-HF, a single factor explained 61% of the variance and Cronbach's alpha was 0.90. The eight item TDS-HF was significantly associated with the thirst intensity score ( r=0.55, p<0.001). Regarding test-retest reliability, the intraclass correlation coefficient was 0.88, and the weighted kappa values ranged from 0.29-0.60. The eight-item TDS-HF is valid and reliable for measuring thirst distress in patients with heart failure.

Heart Failure in Women

PubMed Central

Bozkurt, Biykem; Khalaf, Shaden

2017-01-01

Heart failure is an important cause of morbidity and mortality in women, and they tend to develop it at an older age compared to men. Heart failure with preserved ejection fraction is more common in women than in men and accounts for at least half the cases of heart failure in women. When comparing men and women who have heart failure and a low left ventricular ejection fraction, the women are more symptomatic and have a similarly poor outcome. Overall recommendations for guideline-directed medical therapies show no differences in treatment approaches between men and women. Overall, women are generally underrepresented in clinical trials for heart failure. Further studies are needed to shed light into different mechanisms, causes, and targeted therapies of heart failure in women. PMID:29744014

Role of Transient Receptor Potential Channels in Heart Transplantation: A Potential Novel Therapeutic Target for Cardiac Allograft Vasculopathy.

PubMed

Ma, Shuo; Jiang, Yue; Huang, Weiting; Li, Xintao; Li, Shuzhuang

2017-05-18

Heart transplantation has evolved as the criterion standard therapy for end-stage heart failure, but its efficacy is limited by the development of cardiac allograft vasculopathy (CAV), a unique and rapidly progressive form of atherosclerosis in heart transplant recipients. Here, we briefly review the key processes in the development of CAV during heart transplantation and highlight the roles of transient receptor potential (TRP) channels in these processes during heart transplantation. Understanding the roles of TRP channels in contributing to the key procedures for the development of CAV during heart transplantation could provide basic scientific knowledge for the development of new preventive and therapeutic approaches to manage patients with CAV after heart transplantation.

Blood Pressure Control

NASA Technical Reports Server (NTRS)

1986-01-01

Engineering Development Laboratory developed a system for the cardiovascular study of weightless astronauts. This was designed to aid people with congestive heart failure and diabetes. While in space, astronauts' blood pressure rises, heart rate becomes unstable, and there are sometimes postflight lightheadedness or blackouts. The Baro-Cuff studies the resetting of blood pressure. When a silicone rubber chamber is strapped to the neck, the Baro-Cuff stimulates the carotid arteries by electronically controlled pressure application. Blood pressure controls in patients may be studied.

Evaluation of HRV Biofeedback as a Resilience Building Intervention in the Reserve Component

DTIC Science & Technology

2017-08-01

specific aims of this study are to (1) develop a mobile app for use with the BART protocol; (2) examine the relationship between baseline heart rate...may affect the impact of HRV-BART on resilience, coping, and PTG scale scores. The study team will recruit 500 Reserve Component service members (RCSMs...needed for the study , developed all recruitment materials, and begun data collection and tracking. 15. SUBJECT TERMS Biofeedback, HRV, heart rate

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.

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.

Developing New Treatments for Heart Failure: Focus on the Heart.

PubMed

Gheorghiade, Mihai; Larson, Christopher J; Shah, Sanjiv J; Greene, Stephen J; Cleland, John G F; Colucci, Wilson S; Dunnmon, Preston; Epstein, Stephen E; Kim, Raymond J; Parsey, Ramin V; Stockbridge, Norman; Carr, James; Dinh, Wilfried; Krahn, Thomas; Kramer, Frank; Wahlander, Karin; Deckelbaum, Lawrence I; Crandall, David; Okada, Shunichiro; Senni, Michele; Sikora, Sergey; Sabbah, Hani N; Butler, Javed

2016-05-01

Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF with reduced ejection fraction with the use of agents that block maladaptive neurohormonal pathways. However, during the past decade, with few notable exceptions, the frequency of successful drug development programs has fallen as most novel therapies have failed to offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no therapy has been approved specifically for HF with preserved ejection fraction or for worsening chronic HF (including acutely decompensated HF). Across the spectrum of HF, preliminary results from many phase II trials have been promising but are frequently followed by unsuccessful phase III studies, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials. A major unmet need in HF drug development is the ability to identify homogeneous subsets of patients whose underlying disease is driven by a specific mechanism that can be targeted using a new therapeutic agent. Drug development strategies should increasingly consider therapies that facilitate reverse remodeling by directly targeting the heart itself rather than strictly focusing on agents that unload the heart or target systemic neurohormones. Advancements in cardiac imaging may allow for more focused and direct assessment of drug effects on the heart early in the drug development process. To better understand and address the array of challenges facing current HF drug development, so that future efforts may have a better chance for success, the Food and Drug Administration facilitated a meeting on February 17, 2015, which was attended by clinicians, researchers, regulators, and industry representatives. The following discussion summarizes the key takeaway dialogue from this meeting. © 2016 American Heart Association, Inc.

Endoplasmic reticulum stress sensor protein kinase R-like endoplasmic reticulum kinase (PERK) protects against pressure overload-induced heart failure and lung remodeling.

PubMed

Liu, Xiaoyu; Kwak, Dongmin; Lu, Zhongbing; Xu, Xin; Fassett, John; Wang, Huan; Wei, Yidong; Cavener, Douglas R; Hu, Xinli; Hall, Jennifer; Bache, Robert J; Chen, Yingjie

2014-10-01

Studies have reported that development of congestive heart failure is associated with increased endoplasmic reticulum stress. Double stranded RNA-activated protein kinase R-like endoplasmic reticulum kinase (PERK) is a major transducer of the endoplasmic reticulum stress response and directly phosphorylates eukaryotic initiation factor 2α, resulting in translational attenuation. However, the physiological effect of PERK on congestive heart failure development is unknown. To study the effect of PERK on ventricular structure and function, we generated inducible cardiac-specific PERK knockout mice. Under unstressed conditions, cardiac PERK knockout had no effect on left ventricular mass, or its ratio to body weight, cardiomyocyte size, fibrosis, or left ventricular function. However, in response to chronic transverse aortic constriction, PERK knockout mice exhibited decreased ejection fraction, increased left ventricular fibrosis, enhanced cardiomyocyte apoptosis, and exacerbated lung remodeling in comparison with wild-type mice. PERK knockout also dramatically attenuated cardiac sarcoplasmic reticulum Ca(2+)-ATPase expression in response to aortic constriction. Our findings suggest that PERK is required to protect the heart from pressure overload-induced congestive heart failure. © 2014 American Heart Association, Inc.

Know thy eHealth user: Development of biopsychosocial personas from a study of older adults with heart failure.

PubMed

Holden, Richard J; Kulanthaivel, Anand; Purkayastha, Saptarshi; Goggins, Kathryn M; Kripalani, Sunil

2017-12-01

Personas are a canonical user-centered design method increasingly used in health informatics research. Personas-empirically-derived user archetypes-can be used by eHealth designers to gain a robust understanding of their target end users such as patients. To develop biopsychosocial personas of older patients with heart failure using quantitative analysis of survey data. Data were collected using standardized surveys and medical record abstraction from 32 older adults with heart failure recently hospitalized for acute heart failure exacerbation. Hierarchical cluster analysis was performed on a final dataset of n=30. Nonparametric analyses were used to identify differences between clusters on 30 clustering variables and seven outcome variables. Six clusters were produced, ranging in size from two to eight patients per cluster. Clusters differed significantly on these biopsychosocial domains and subdomains: demographics (age, sex); medical status (comorbid diabetes); functional status (exhaustion, household work ability, hygiene care ability, physical ability); psychological status (depression, health literacy, numeracy); technology (Internet availability); healthcare system (visit by home healthcare, trust in providers); social context (informal caregiver support, cohabitation, marital status); and economic context (employment status). Tabular and narrative persona descriptions provide an easy reference guide for informatics designers. Personas development using approaches such as clustering of structured survey data is an important tool for health informatics professionals. We describe insights from our study of patients with heart failure, then recommend a generic ten-step personas development process. Methods strengths and limitations of the study and of personas development generally are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of ECG sampling rate in fetal heart rate variability analysis.

PubMed

De Jonckheere, J; Garabedian, C; Charlier, P; Champion, C; Servan-Schreiber, E; Storme, L; Debarge, V; Jeanne, M; Logier, R

2017-07-01

Fetal hypoxia results in a fetal blood acidosis (pH<;7.10). In such a situation, the fetus develops several adaptation mechanisms regulated by the autonomic nervous system. Many studies demonstrated significant changes in heart rate variability in hypoxic fetuses. So, fetal heart rate variability analysis could be of precious help for fetal hypoxia prediction. Commonly used fetal heart rate variability analysis methods have been shown to be sensitive to the ECG signal sampling rate. Indeed, a low sampling rate could induce variability in the heart beat detection which will alter the heart rate variability estimation. In this paper, we introduce an original fetal heart rate variability analysis method. We hypothesize that this method will be less sensitive to ECG sampling frequency changes than common heart rate variability analysis methods. We then compared the results of this new heart rate variability analysis method with two different sampling frequencies (250-1000 Hz).

The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development.

PubMed

Huang, Wen; Deng, Yun; Dong, Wei; Yuan, Wuzhou; Wan, Yongqi; Mo, Xiaoyan; Li, Yongqing; Wang, Zequn; Wang, Yuequn; Ocorr, Karen; Zhang, Bo; Lin, Shuo; Wu, Xiushan

2011-02-01

In order to study the impalpable effect of GFP in homozygous heart-specific GFP-positive zebrafish during the early stage, the researchers analyzed the heart function of morphology and physiology at the first 3 days after fertilization. This zebrafish line was produced by a large-scale Tol2 transposon mediated enhancer trap screen that generated a transgenic zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer. In situ hybridization experiments showed that the nppa:GFP line faithfully recapitulated both the spatial and temporal expressions of the endogenous nppa. Green fluorescence was intensively and specifically expressed in the myocardial cells located both in the heart chambers and in the atrioventricular canal. The embryonic heart of nppa:GFP line developed normally compared with those in the wild type. There was no difference between the nappa:GFP and wild type lines with respect to heart rate, overall size, ejection volume, and fractional shortening. Thus the excess expression of GFP in this transgenic line seemed to exert no detrimental effects on zebrafish hearts during the early stages.

Genetic and flow anomalies in congenital heart disease.

PubMed

Rugonyi, Sandra

2016-01-01

Congenital heart defects are the most common malformations in humans, affecting approximately 1% of newborn babies. While genetic causes of congenital heart disease have been studied, only less than 20% of human cases are clearly linked to genetic anomalies. The cause for the majority of the cases remains unknown. Heart formation is a finely orchestrated developmental process and slight disruptions of it can lead to severe malformations. Dysregulation of developmental processes leading to heart malformations are caused by genetic anomalies but also environmental factors including blood flow. Intra-cardiac blood flow dynamics plays a significant role regulating heart development and perturbations of blood flow lead to congenital heart defects in animal models. Defects that result from hemodynamic alterations, however, recapitulate those observed in human babies, even those due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental events, such as valve formation and septation, occur under blood flow conditions while the heart is pumping, blood flow regulation of cardiac formation might be a critical factor determining cardiac phenotype. The contribution of flow to cardiac phenotype, however, is frequently ignored. More research is needed to determine how blood flow influences cardiac development and the extent to which flow may determine cardiac phenotype.

[Congenital heart disease mortality in Spain during a 10 year period (2003-2012)].

PubMed

Pérez-Lescure Picarzo, Javier; Mosquera González, Margarita; Latasa Zamalloa, Pello; Crespo Marcos, David

2018-05-01

Congenital heart disease is a major cause of infant mortality in developed countries. In Spain, there are no publications at national level on mortality due to congenital heart disease. The aim of this study is to analyse mortality in infants with congenital heart disease, lethality of different types of congenital heart disease, and their variation over a ten-year period. A retrospective observational study was performed to evaluate mortality rate of children under one year old with congenital heart disease, using the minimum basic data set, from 2003 to 2012. Mortality rate and relative risk of mortality were estimated by Poisson regression. There were 2,970 (4.58%) infant deaths in a population of 64,831 patients with congenital heart disease, with 73.8% of deaths occurring during first week of life. Infant mortality rate in patients with congenital heart disease was 6.23 per 10,000 live births, and remained constant during the ten-year period of the study, representing 18% of total infant mortality rate in Spain. The congenital heart diseases with highest mortality rates were hypoplastic left heart syndrome (41.4%), interruption of aortic arch (20%), and total anomalous pulmonary drainage (16.8%). Atrial septal defect (1%) and pulmonary stenosis (1.1%) showed the lowest mortality rate. Congenital heart disease was a major cause of infant mortality with no variations during the study period. The proportion of infants who died in our study was similar to other similar countries. In spite of current medical advances, some forms of congenital heart disease show very high mortality rates. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Changes in dynamic embryonic heart wall motion in response to outflow tract banding measured using video densitometry

NASA Astrophysics Data System (ADS)

Stovall, Stephanie; Midgett, Madeline; Thornburg, Kent; Rugonyi, Sandra

2016-11-01

Abnormal blood flow during early cardiovascular development has been identified as a key factor in the pathogenesis of congenital heart disease; however, the mechanisms by which altered hemodynamics induce cardiac malformations are poorly understood. This study used outflow tract (OFT) banding to model increased afterload, pressure, and blood flow velocities at tubular stages of heart development and characterized the immediate changes in cardiac wall motion due to banding in chicken embryo models with light microscopy-based video densitometry. Optical videos were used to acquire two-dimensional heart image sequences over the cardiac cycle, from which intensity data were extracted along the heart centerline at several locations in the heart ventricle and OFT. While no changes were observed in the synchronous contraction of the ventricle with banding, the peristaltic-like wall motion in the OFT was significantly affected. Our data provide valuable insight into early cardiac biomechanics and its characterization using a simple light microscopy-based imaging modality.

Investigating the Flow and Biomechanics of the Embryonic Zebrafish Heart

NASA Astrophysics Data System (ADS)

Johnson, Brennan; Garrity, Deborah; Dasi, Lakshmi

2010-11-01

Understanding flow and kinematic characteristics of the embryonic heart is a prerequisite to devise early intervention or detection methods in the context of congenital heart defects. In this study, the kinematics and fluid dynamics of the embryonic zebrafish heart were analyzed through the early stages of cardiac development (24-48 hours post-fertilization) in vivo using optical microscopy and high-speed video. Endocardial walls and individual blood cells were segmented from raw images and were tracked through the cardiac cycle. Particle tracking velocimetry analysis yielded quantitative blood cell velocity field, chamber volume, and flow rate information. It was seen that the pumping mechanism starts as a combined peristaltic and suction pump while the heart is in the tube configuration and transforms into a positive displacement pump after cardiac looping. Strong two-phase nature of the fluid is evident. This work provides us new understanding of the spatio-temporal characteristics of kinematics and blood cell velocity field inside the developing heart.

[New markers of progression of chronic heart failure in patients with myocardial infarction, type 2 diabetes and obesity].

PubMed

Kravchun, P P; Kadykova, O I; Gabisonia, T N

2015-01-01

Currently identified a large number of biomarkers that are closely linked with the development of chronic heart failure, some of which are clusterin and fractalkine. Accordingly, the purpose of our study was - to evaluate the role of clusterin and fractalkine in progression of chronic heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. We investigated 71 patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. All patients with postinfarction cardiosclerosis, diabetes and obesity were divided into groups according to the functional class of chronic heart failure (CHF). It was found that an increase the level of fractalkine and reduced clusterin leads due to the development of systolic dysfunction and heart failure progression in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. Fractalkine and clusterin play an important role in progression of the heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity, and this gives them the right to be considered indicators of the severity of CHF.

Infant diet, gender and the normative development of vagal tone and heart period during the first two years of life

USDA-ARS?s Scientific Manuscript database

Relationships between early postnatal diet and the development of cardiac regulation were studied using resting vagal tone and heart period measures obtained quarterly during infancy and at 2 years in 158 breast-fed, 159 milk formula-fed, and 148 soy formula-fed infants. Both measures increased acro...

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart.

PubMed

Poelmann, Robert E; Gittenberger-de Groot, Adriana C; Biermans, Marcel W M; Dolfing, Anne I; Jagessar, Armand; van Hattum, Sam; Hoogenboom, Amanda; Wisse, Lambertus J; Vicente-Steijn, Rebecca; de Bakker, Merijn A G; Vonk, Freek J; Hirasawa, Tatsuya; Kuratani, Shigeru; Richardson, Michael K

2017-01-01

Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. We studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population) forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard) or it is vestigial (turtle). Crocodiles are unique in bearing a central shunt, the foramen of Panizza, between the roots of both aortae. Finally, the soft-shell turtle investigated here exhibits a spongy histology of the developing carotid arteries supposedly related to regulation of blood flow during pharyngeal excretion in this species. This is the first time that is shown that an interplay of second heart field-derived flow dividers with a neural crest-derived cell population is a variable but common, denominator across all species studied for vascular patterning and outflow tract septation. The observed differences in normal development of reptiles may have impact on the understanding of development of human congenital outflow tract malformations.

The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

PubMed

Piven, Oksana O; Winata, Cecilia L

2017-12-01

The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the mechanism by which the canonical Wnt signaling regulates development of the heart and its regeneration after damage.

Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study.

PubMed

Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

2016-02-09

To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Case control study. An Iranian referral university hospital. 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

CHARACTERIZING THE ROLE OF THE NELL1 GENE IN CARDIOVASCULAR DEVELOPMENT

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

Liu, L. Y.; Culiat, C.

Nell1{sup 6R} is a chemically-induced point mutation in a novel cell-signaling gene, Nell1, which results in truncation of the protein and degradation of the Nell16R transcript. Earlier studies revealed that loss of Nell1 function reduces expression of numerous extracellular matrix (ECM) proteins required for differentiation of bone and cartilage precursor cells, thereby causing severe skull and spinal defects. Since skeletal and cardiovascular development are closely linked biological processes, this research focused on: a) examining Nell16R mutant mice for cardiovascular defects, b) determining Nell1 expression in fetal and adult hearts, and c) establishing how ECM genes affected by Nell1 infl uencemore » heart development. Structural heart defects in Nell16R mutant fetuses were analyzed by heart length and width measurements and standard histological methods (haematoxylin and eosin staining). Nell1 expression was assayed in fetal and adult hearts using reverse transcription polymerase chain reaction (RT-PCR). A comprehensive bioinformatics analysis using public databases (Stanford SOURCE Search, Integrated Cartilage Gene Database, Mouse Genome Informatics, and NCBI UniGene) was undertaken to investigate the relationship between cardiovascular development and each of twentyeight genes affected by Nell1. Nell1-defi cient mice have signifi cantly enlarged hearts (particularly the heart width), dramatically reduced blood fl ow out of the heart and unexpanded lungs. Isolation of total RNAs from hearts of adult (control and heterozygote) and fetal (control and homozygous mutant) mice have been completed and RT-PCR assays are in progress. The bioinformatics analysis showed that the majority of genes with reduced expression in Nell1-defi cient mice are normally expressed in the heart (79%; 22/28), blood vessels (71%; 20/28) and bone marrow (61%; 17/28). Moreover, mouse mutations in seven of these genes (Col15a1, Osf-2, Bmpr1a, Pkd1, Mfge8, Ptger4, Col5a1) manifest abnormalities in cardiovascular development. These data demonstrate for the fi rst time that Nell1 has a role in early mammalian cardiovascular development, mediated by its regulation of ECM proteins necessary for normal cell growth and differentiation. In addition, understanding the mechanisms by which Nell1 and its associated ECM genes affect the cardiovascular system can provide future strategies for the treatment of heart and blood vessel defects.« less

Pulsatile support using a rotary left ventricular assist device with an electrocardiography-synchronized rotational speed control mode for tracking heart rate variability.

PubMed

Arakawa, Mamoru; Nishimura, Takashi; Takewa, Yoshiaki; Umeki, Akihide; Ando, Masahiko; Kishimoto, Yuichiro; Kishimoto, Satoru; Fujii, Yutaka; Date, Kazuma; Kyo, Shunei; Adachi, Hideo; Tatsumi, Eisuke

2016-06-01

We previously developed a novel control system for a continuous-flow left ventricular assist device (LVAD), the EVAHEART, and demonstrated that sufficient pulsatility can be created by increasing its rotational speed in the systolic phase (pulsatile mode) in a normal heart animal model. In the present study, we assessed this system in its reliability and ability to follow heart rate variability. We implanted an EVAHEART via left thoracotomy into five goats for the Study for Fixed Heart Rate with ventricular pacing at 80, 100, 120 and 140 beats/min and six goats for the Study for native heart rhythm. We tested three modes: the circuit clamp, the continuous mode and the pulsatile mode. In the pulsatile mode, rotational speed was increased during the initial 35 % of the RR interval by automatic control based on the electrocardiogram. Pulsatility was evaluated by pulse pressure and dP/dt max of aortic pressure. As a result, comparing the pulsatile mode with the continuous mode, the pulse pressure was 28.5 ± 5.7 vs. 20.3 ± 7.9 mmHg, mean dP/dt max was 775.0 ± 230.5 vs 442.4 ± 184.7 mmHg/s at 80 bpm in the study for fixed heart rate, respectively (P < 0.05). The system successfully determined the heart rate to be 94.6 % in native heart rhythm. Furthermore, pulse pressure was 41.5 ± 7.9 vs. 27.8 ± 5.6 mmHg, mean dP/dt max was 716.2 ± 133.9 vs 405.2 ± 86.0 mmHg/s, respectively (P < 0.01). In conclusion, our newly developed the pulsatile mode for continuous-flow LVADs reliably provided physiological pulsatility with following heart rate variability.

Open heart surgery in Nigeria; a work in progress.

PubMed

Falase, Bode; Sanusi, Michael; Majekodunmi, Adetinuwe; Animasahun, Barakat; Ajose, Ifeoluwa; Idowu, Ariyo; Oke, Adewale

2013-01-12

There has been limited success in establishing Open Heart Surgery programmes in Nigeria despite the high prevalence of structural heart disease and the large number of Nigerian patients that travel abroad for Open Heart Surgery. The challenges and constraints to the development of Open Heart Surgery in Nigeria need to be identified and overcome. The aim of this study is to review the experience with Open Heart Surgery at the Lagos State University Teaching Hospital and highlight the challenges encountered in developing this programme. This is a retrospective study of patients that underwent Open Heart Surgery in our institution. The source of data was a prospectively maintained database. Extracted data included patient demographics, indication for surgery, euroscore, cardiopulmonary bypass time, cross clamp time, complications and patient outcome. 51 Open Heart Surgery procedures were done between August 2004 and December 2011. There were 21 males and 30 females. Mean age was 29 ± 15.6 years. The mean euroscore was 3.8 ± 2.1. The procedures done were Mitral Valve Replacement in 15 patients (29.4%), Atrial Septal Defect Repair in 14 patients (27.5%), Ventricular Septal Defect Repair in 8 patients (15.7%), Aortic Valve Replacement in 5 patients (9.8%), excision of Left Atrial Myxoma in 2 patients (3.9%), Coronary Artery Bypass Grafting in 2 patients (3.9%), Bidirectional Glenn Shunts in 2 patients (3.9%), Tetralogy of Fallot repair in 2 patients (3.9%) and Mitral Valve Repair in 1 patient (2%). There were 9 mortalities (17.6%) in this series. Challenges encountered included the low volume of cases done, an unstable working environment, limited number of trained staff, difficulty in obtaining laboratory support, limited financial support and difficulty in moving away from the Cardiac Mission Model. The Open Heart Surgery program in our institution is still being developed but the identified challenges need to be overcome if this program is to be sustained. Similar challenges will need to be overcome by other cardiac stakeholders if other OHS programs are to be developed and sustained in Nigeria.

Implantable Hemodynamic Monitoring for Heart Failure Patients.

PubMed

Abraham, William T; Perl, Leor

2017-07-18

Rates of heart failure hospitalization remain unacceptably high. Such hospitalizations are associated with substantial patient, caregiver, and economic costs. Randomized controlled trials of noninvasive telemedical systems have failed to demonstrate reduced rates of hospitalization. The failure of these technologies may be due to the limitations of the signals measured. Intracardiac and pulmonary artery pressure-guided management has become a focus of hospitalization reduction in heart failure. Early studies using implantable hemodynamic monitors demonstrated the potential of pressure-based heart failure management, whereas subsequent studies confirmed the clinical utility of this approach. One large pivotal trial proved the safety and efficacy of pulmonary artery pressure-guided heart failure management, showing a marked reduction in heart failure hospitalizations in patients randomized to active pressure-guided management. "Next-generation" implantable hemodynamic monitors are in development, and novel approaches for the use of this data promise to expand the use of pressure-guided heart failure management. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale.

PubMed

Rose, Beth A; Force, Thomas; Wang, Yibin

2010-10-01

Among the myriad of intracellular signaling networks that govern the cardiac development and pathogenesis, mitogen-activated protein kinases (MAPKs) are prominent players that have been the focus of extensive investigations in the past decades. The four best characterized MAPK subfamilies, ERK1/2, JNK, p38, and ERK5, are the targets of pharmacological and genetic manipulations to uncover their roles in cardiac development, function, and diseases. However, information reported in the literature from these efforts has not yet resulted in a clear view about the roles of specific MAPK pathways in heart. Rather, controversies from contradictive results have led to a perception that MAPKs are ambiguous characters in heart with both protective and detrimental effects. The primary object of this review is to provide a comprehensive overview of the current progress, in an effort to highlight the areas where consensus is established verses the ones where controversy remains. MAPKs in cardiac development, cardiac hypertrophy, ischemia/reperfusion injury, and pathological remodeling are the main focuses of this review as these represent the most critical issues for evaluating MAPKs as viable targets of therapeutic development. The studies presented in this review will help to reveal the major challenges in the field and the limitations of current approaches and point to a critical need in future studies to gain better understanding of the fundamental mechanisms of MAPK function and regulation in the heart.

Cardiac image modelling: Breadth and depth in heart disease.

PubMed

Suinesiaputra, Avan; McCulloch, Andrew D; Nash, Martyn P; Pontre, Beau; Young, Alistair A

2016-10-01

With the advent of large-scale imaging studies and big health data, and the corresponding growth in analytics, machine learning and computational image analysis methods, there are now exciting opportunities for deepening our understanding of the mechanisms and characteristics of heart disease. Two emerging fields are computational analysis of cardiac remodelling (shape and motion changes due to disease) and computational analysis of physiology and mechanics to estimate biophysical properties from non-invasive imaging. Many large cohort studies now underway around the world have been specifically designed based on non-invasive imaging technologies in order to gain new information about the development of heart disease from asymptomatic to clinical manifestations. These give an unprecedented breadth to the quantification of population variation and disease development. Also, for the individual patient, it is now possible to determine biophysical properties of myocardial tissue in health and disease by interpreting detailed imaging data using computational modelling. For these population and patient-specific computational modelling methods to develop further, we need open benchmarks for algorithm comparison and validation, open sharing of data and algorithms, and demonstration of clinical efficacy in patient management and care. The combination of population and patient-specific modelling will give new insights into the mechanisms of cardiac disease, in particular the development of heart failure, congenital heart disease, myocardial infarction, contractile dysfunction and diastolic dysfunction. Copyright © 2016. Published by Elsevier B.V.

Deficient maternal zinc intake-but not folate-is associated with lower fetal heart rate variability.

PubMed

Spann, Marisa N; Smerling, Jennifer; Gustafsson, Hanna; Foss, Sophie; Altemus, Margaret; Monk, Catherine

2015-03-01

Few studies of maternal prenatal diet and child development examine micronutrient status in relation to fetal assessment. Twenty-four-hour dietary recall of zinc and folate and 20min of fetal heart rate were collected from 3rd trimester pregnant adolescents. Deficient zinc was associated with less fetal heart rate variability. Deficient folate had no associations with HRV. Neither deficient zinc nor deficient folate was related to fetal heart rate. These findings, from naturalistic observation, are consistent with emerging data on prenatal zinc supplementation using a randomized control design. Taken together, the findings suggest that maternal prenatal zinc intake is an important and novel factor for understanding child ANS development. Copyright © 2015. Published by Elsevier Ireland Ltd.

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.

The Popeye domain containing 2 (popdc2) gene in zebrafish is required for heart and skeletal muscle development

PubMed Central

Kirchmaier, Bettina C.; Poon, Kar Lai; Schwerte, Thorsten; Huisken, Jan; Winkler, Christoph; Jungblut, Benno; Stainier, Didier Y.; Brand, Thomas

2013-01-01

The Popeye domain containing (Popdc) genes encode a family of transmembrane proteins with an evolutionary conserved Popeye domain. These genes are abundantly expressed in striated muscle tissue, however their function is not well understood. In this study we have investigated the role of the popdc2 gene in zebrafish. Popdc2 transcripts were detected in the embryonic myocardium and transiently in the craniofacial and tail musculature. Morpholino oligonucleotide-mediated knockdown of popdc2 resulted in aberrant development of skeletal muscle and heart. Muscle segments in the trunk were irregularly shaped and craniofacial muscles were severely reduced or even missing. In the heart, pericardial edema was prevalent in the morphants and heart chambers were elongated and looping was abnormal. These pathologies in muscle and heart were alleviated after reducing the morpholino concentration. However the heart still was abnormal displaying cardiac arrhythmia at later stages of development. Optical recordings of cardiac contractility revealed irregular ventricular contractions with a 2:1, or 3:1 atrial/ventricular conduction ratio, which caused a significant reduction in heart frequency. Recordings of calcium transients with high spatiotemporal resolution using a transgenic calcium indicator line (Tg(cmlc2:gCaMP)s878) and SPIM microscopy confirmed the presence of a severe arrhythmia phenotype. Our results identify popdc2 as a gene important for striated muscle differentiation and cardiac morphogenesis. In addition it is required for the development of the cardiac conduction system. PMID:22290329

Heart Rate Profiles of Children with and without Autism Spectrum Disorder in Response to Physical Play: A Preliminary Investigation

ERIC Educational Resources Information Center

Breslin, Casey M.; Rudisill, Mary E.; Wadsworth, Danielle W.

2015-01-01

In this study, the heart rate response of children with and without autism spectrum disorder (ASD) exposed to outdoor free play sessions during preschool was examined. Participants (n = 7; four children with ASD and three children who show typical development) wore Actiheart heart rate monitors during 6 school days. Using a single-subject design,…

Drosophila as a model to study cardiac aging

PubMed Central

Nishimura, Mayuko; Ocorr, Karen; Bodmer, Rolf; Cartry, Jérôme

2010-01-01

With age, cardiac performance declines progressively and the risk of heart disease, a primary cause of mortality, rises dramatically. As the elderly population continues to increase, it is critical to gain a better understanding of the genetic influences and modulatory factors that impact cardiac aging. In an attempt to determine the relevance and utility of the Drosophila heart in unraveling the genetic mechanisms underlying cardiac aging, a variety of heart performance assays have recently been developed to quantify Drosophila heart performance that permit the use of the fruit fly to investigate the heart’s decline with age. As for the human heart, Drosophila heart function also deteriorates with age. Notably, with progressive age the incidence of cardiac arrhythmias, myofibrillar disorganization and susceptibility to heart dysfunction and failure all increase significantly. We review here the evidence for an involvement of the insulin-TOR pathway, the KATP channel subunit dSur, the KCNQ potassium channel, as well as Dystrophin and Myosin in fly cardiac aging, and discuss the utility of the Drosophila heart model for cardiac aging studies. PMID:21130861

Heart Development, Diseases, and Regeneration　- New Approaches From Innervation, Fibroblasts, and Reprogramming.

PubMed

Ieda, Masaki

2016-09-23

It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081-2088).

Confocal Imaging of Early Heart Development in Xenopus laevis

PubMed Central

Kolker, Sandra J.; Tajchman, Urszula; Weeks, Daniel L.

2013-01-01

Xenopus laevis provides a number of advantages for studies on cardiovascular development. The embryos are fairly large, easy to obtain, and can develop at ambient temperature in simple buffer solutions. Although classic descriptions of heart development exist, the ability to use whole mount immunohistochemical methods and confocal microscopy may enhance the ability to understand both normal and experimentally perturbed cardiovascular development. We have started to examine the early stages of cardiac development in Xenopus, seeking to identify antibodies and fixatives that allow easy examination of the developing heart. We have used monoclonal antibodies (mAbs) raised against bovine cardiac troponin T and chicken tropomyosin to visualize cardiac muscle, a goat antibody recognizing bovine type VI collagen to stain the lining of vessels, and the JB3 mAb raised against chicken fibrillin which allows the visualization of a variety of cardiovascular tissues during early development. Results from embryonic stages 24–46 are presented. PMID:10644411

Heart check: the development and evolution of an organizational heart health assessment.

PubMed

Golaszewski, Thomas; Fisher, Brian

2002-01-01

The purpose of this article is to document the development, testing, and application of an organizational assessment tool used to measure employer support for heart health. Additional information is presented on its future research and applications plan. This article represents the pooling of results from multiple studies using a variety of designs, including pilot tests, cross-sectional analyses, and quasi-experiments. Worksites covering the spectrum of employers across industry types and size, and throughout all of New York State. Over 10,000 New York employees and 1000 New York employers are represented in the multiple phases of this research. Heart Check is a 226-item inventory designed to measure such features in the worksite as organizational foundations, administrative supports, tobacco control, nutrition support, physical activity support, stress management, screening services, and company demographics. Additional side studies used professional judgments and behavioral surveys. As an assessment tool Heart Check shows evidence for reliability and validity. Applications of the instrument show characteristics that define high-scoring companies, quasi standards for New York employers, and, when applied during interventions, positive changes in organizational support levels. A relatively inexpensive, easy-to-use, and metrically tested instrument exists for measuring the construct of organizational support for employee heart health. The instrument shows promise as part of a system to enhance heart health through public health-based interventions in the workplace.

Development and preliminary evaluation of an Android based heart rate variability biofeedback system.

PubMed

Abtahi, F; Berndtsson, A; Abtahi, S; Seoane, F; Lindecrantz, K

2014-01-01

The reduced Heart Rate Variability (HRV) is believed to be associated with several diseases such as congestive heart failure, diabetes and chronic kidney diseases (CKD). In these cases, HRV biofeedback may be a potential intervention method to increase HRV which in turn is beneficial to these patients. In this work, a real-time Android biofeedback application based on a Bluetooth enabled ECG and thoracic electrical bioimpedance (respiration) measurement device has been developed. The system performance and usability have been evaluated in a brief study with eight healthy volunteers. The result demonstrates real-time performance of system and positive effects of biofeedback training session by increased HRV and reduced heart rate. Further development of the application and training protocol is ongoing to investigate duration of training session to find an optimum length and interval of biofeedback sessions to use in potential interventions.

The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.

PubMed

Pahnke, Aric; Conant, Genna; Huyer, Locke Davenport; Zhao, Yimu; Feric, Nicole; Radisic, Milica

2016-05-06

Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models. Copyright © 2015 Elsevier Inc. All rights reserved.

Health Gain through Screening--Coronary Heart Disease and Stroke: Developing Primary Health Care Services for People with Intellectual Disability.

ERIC Educational Resources Information Center

Wells, M. B.; Turner, S.; Martin, D. M.; Roy, A.

1997-01-01

A study of 120 British adults with intellectual disability found they had higher risk factors of developing coronary heart disease and stroke than the general population. There was a greater incidence of obesity and considerably lower physical activity levels than the general population. Several also had abnormal cholesterol readings. (CR)

ChIP-seq Identification of Weakly Conserved Heart Enhancers

PubMed Central

Blow, Matthew J.; McCulley, David J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Bristow, James; Ren, Bing; Black, Brian L.; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2011-01-01

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of heart enhancers. Here we used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over three thousand candidate heart enhancers genome-wide. Compared to other tissues studied at this time-point, most candidate heart enhancers are less deeply conserved in vertebrate evolution. Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary constraint of embryonic enhancers can vary depending on tissue type. PMID:20729851

Cell-accurate optical mapping across the entire developing heart.

PubMed

Weber, Michael; Scherf, Nico; Meyer, Alexander M; Panáková, Daniela; Kohl, Peter; Huisken, Jan

2017-12-29

Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca 2+ -mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs.

Cell-accurate optical mapping across the entire developing heart

PubMed Central

Meyer, Alexander M; Panáková, Daniela; Kohl, Peter

2017-01-01

Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca2+-mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs. PMID:29286002

Rheumatic fever and rheumatic heart disease in developing countries

PubMed Central

Padmavati, S.

1978-01-01

Studies on the prevalence and other epidemiological features of rheumatic fever and rheumatic heart disease and pilot prophylactic programmes have been carried out in India for the past 12 years or more. The results of these, together with data from other developing countries, have been taken into account in discussing the problems of these diseases in the developing world. Suggestions for their control, to be modified according to local conditions, are made. PMID:310360

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.

Expression of cardiac neural crest and heart genes isolated by modified differential display.

PubMed

Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

2003-08-01

The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

Exploratory study into the awareness of heart diseases among Emirati women (UAE) and their health seeking behaviour- a qualitative study.

PubMed

Khan, Sarah; Khoory, Ayesha; Al Zaffin, Dhabia; Al Suwaidi, Meera

2016-11-07

Cardiovascular diseases were the leading cause of death in women in the United Arab Emirates (UAE) in 2010. The UAE is expected to experience a tripling of heart diseases in the next two decades as risk factors for heart diseases increase. Research shows that first year survival rates of younger women suffering from a heart attack are lower than in men. Women present with a wider range of symptoms for heart diseases than men; non-recognition of atypical symptoms may explain the delay in seeking treatment and poor prognosis following heart diseases in women. No known study on awareness of heart diseases among women has been carried out in the Middle Eastern region. Social constructionist and interpretivist epistemological approaches have been considered in this qualitative study to explore the awareness of heart diseases and the health seeking behavior of Emirati women. Convenience sampling was used to recruit 41 Emirati women. Three focus groups and six in-depth semi-structured interviews were conducted to obtain data. Thematic content analysis was applied to the data following transcription and translation of recordings. Emirati women had limited knowledge on heart diseases. Women were generally unaware of the atypical symptoms, commonly experienced by women however they identified most risk factors associated with heart diseases. Lack of awareness of disease severity and symptoms, sociocultural influences and distrust in the healthcare system were considered the main barriers to seeking prompt treatment. This study clearly identified gaps and inaccuracies in knowledge of heart diseases, which could contribute to delayed health seeking action and possibly poorer prognosis among Emirati women. Absence of initiatives to educate women on cardiovascular diseases in UAE has erroneously deemed it a less serious concern among Emirati women. The findings from this study provide clear indications of the need to increase accountability of the healthcare system and to develop culturally relevant, gender specific, age focused, heart diseases related public health awareness campaigns in UAE.

Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

PubMed

Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

2017-07-01

Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously undiscovered changes in myofibrillar power output were found and were associated with alterations in myofilament proteins, providing potential new targets to exploit for improved ventricular pump function in heart failure. Copyright © 2017 the American Physiological Society.

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

PubMed

den Hoed, Marcel; Eijgelsheim, Mark; Esko, Tõnu; Brundel, Bianca J J M; Peal, David S; Evans, David M; Nolte, Ilja M; Segrè, Ayellet V; Holm, Hilma; Handsaker, Robert E; Westra, Harm-Jan; Johnson, Toby; Isaacs, Aaron; Yang, Jian; Lundby, Alicia; Zhao, Jing Hua; Kim, Young Jin; Go, Min Jin; Almgren, Peter; Bochud, Murielle; Boucher, Gabrielle; Cornelis, Marilyn C; Gudbjartsson, Daniel; Hadley, David; van der Harst, Pim; Hayward, Caroline; den Heijer, Martin; Igl, Wilmar; Jackson, Anne U; Kutalik, Zoltán; Luan, Jian'an; Kemp, John P; Kristiansson, Kati; Ladenvall, Claes; Lorentzon, Mattias; Montasser, May E; Njajou, Omer T; O'Reilly, Paul F; Padmanabhan, Sandosh; St Pourcain, Beate; Rankinen, Tuomo; Salo, Perttu; Tanaka, Toshiko; Timpson, Nicholas J; Vitart, Veronique; Waite, Lindsay; Wheeler, William; Zhang, Weihua; Draisma, Harmen H M; Feitosa, Mary F; Kerr, Kathleen F; Lind, Penelope A; Mihailov, Evelin; Onland-Moret, N Charlotte; Song, Ci; Weedon, Michael N; Xie, Weijia; Yengo, Loic; Absher, Devin; Albert, Christine M; Alonso, Alvaro; Arking, Dan E; de Bakker, Paul I W; Balkau, Beverley; Barlassina, Cristina; Benaglio, Paola; Bis, Joshua C; Bouatia-Naji, Nabila; Brage, Søren; Chanock, Stephen J; Chines, Peter S; Chung, Mina; Darbar, Dawood; Dina, Christian; Dörr, Marcus; Elliott, Paul; Felix, Stephan B; Fischer, Krista; Fuchsberger, Christian; de Geus, Eco J C; Goyette, Philippe; Gudnason, Vilmundur; Harris, Tamara B; Hartikainen, Anna-Liisa; Havulinna, Aki S; Heckbert, Susan R; Hicks, Andrew A; Hofman, Albert; Holewijn, Suzanne; Hoogstra-Berends, Femke; Hottenga, Jouke-Jan; Jensen, Majken K; Johansson, Asa; Junttila, Juhani; Kääb, Stefan; Kanon, Bart; Ketkar, Shamika; Khaw, Kay-Tee; Knowles, Joshua W; Kooner, Angrad S; Kors, Jan A; Kumari, Meena; Milani, Lili; Laiho, Päivi; Lakatta, Edward G; Langenberg, Claudia; Leusink, Maarten; Liu, Yongmei; Luben, Robert N; Lunetta, Kathryn L; Lynch, Stacey N; Markus, Marcello R P; Marques-Vidal, Pedro; Mateo Leach, Irene; McArdle, Wendy L; McCarroll, Steven A; Medland, Sarah E; Miller, Kathryn A; Montgomery, Grant W; Morrison, Alanna C; Müller-Nurasyid, Martina; Navarro, Pau; Nelis, Mari; O'Connell, Jeffrey R; O'Donnell, Christopher J; Ong, Ken K; Newman, Anne B; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P; Psaty, Bruce M; Rao, Dabeeru C; Ring, Susan M; Rossin, Elizabeth J; Rudan, Diana; Sanna, Serena; Scott, Robert A; Sehmi, Jaban S; Sharp, Stephen; Shin, Jordan T; Singleton, Andrew B; Smith, Albert V; Soranzo, Nicole; Spector, Tim D; Stewart, Chip; Stringham, Heather M; Tarasov, Kirill V; Uitterlinden, André G; Vandenput, Liesbeth; Hwang, Shih-Jen; Whitfield, John B; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilson, James F; Witteman, Jacqueline C M; Wong, Andrew; Wong, Quenna; Jamshidi, Yalda; Zitting, Paavo; Boer, Jolanda M A; Boomsma, Dorret I; Borecki, Ingrid B; van Duijn, Cornelia M; Ekelund, Ulf; Forouhi, Nita G; Froguel, Philippe; Hingorani, Aroon; Ingelsson, Erik; Kivimaki, Mika; Kronmal, Richard A; Kuh, Diana; Lind, Lars; Martin, Nicholas G; Oostra, Ben A; Pedersen, Nancy L; Quertermous, Thomas; Rotter, Jerome I; van der Schouw, Yvonne T; Verschuren, W M Monique; Walker, Mark; Albanes, Demetrius; Arnar, David O; Assimes, Themistocles L; Bandinelli, Stefania; Boehnke, Michael; de Boer, Rudolf A; Bouchard, Claude; Caulfield, W L Mark; Chambers, John C; Curhan, Gary; Cusi, Daniele; Eriksson, Johan; Ferrucci, Luigi; van Gilst, Wiek H; Glorioso, Nicola; de Graaf, Jacqueline; Groop, Leif; Gyllensten, Ulf; Hsueh, Wen-Chi; Hu, Frank B; Huikuri, Heikki V; Hunter, David J; Iribarren, Carlos; Isomaa, Bo; Jarvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kiemeney, Lambertus A; van der Klauw, Melanie M; Kooner, Jaspal S; Kraft, Peter; Iacoviello, Licia; Lehtimäki, Terho; Lokki, Marja-Liisa L; Mitchell, Braxton D; Navis, Gerjan; Nieminen, Markku S; Ohlsson, Claes; Poulter, Neil R; Qi, Lu; Raitakari, Olli T; Rimm, Eric B; Rioux, John D; Rizzi, Federica; Rudan, Igor; Salomaa, Veikko; Sever, Peter S; Shields, Denis C; Shuldiner, Alan R; Sinisalo, Juha; Stanton, Alice V; Stolk, Ronald P; Strachan, David P; Tardif, Jean-Claude; Thorsteinsdottir, Unnur; Tuomilehto, Jaako; van Veldhuisen, Dirk J; Virtamo, Jarmo; Viikari, Jorma; Vollenweider, Peter; Waeber, Gérard; Widen, Elisabeth; Cho, Yoon Shin; Olsen, Jesper V; Visscher, Peter M; Willer, Cristen; Franke, Lude; Erdmann, Jeanette; Thompson, John R; Pfeufer, Arne; Sotoodehnia, Nona; Newton-Cheh, Christopher; Ellinor, Patrick T; Stricker, Bruno H Ch; Metspalu, Andres; Perola, Markus; Beckmann, Jacques S; Smith, George Davey; Stefansson, Kari; Wareham, Nicholas J; Munroe, Patricia B; Sibon, Ody C M; Milan, David J; Snieder, Harold; Samani, Nilesh J; Loos, Ruth J F

2013-06-01

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders

PubMed Central

den Hoed, Marcel; Eijgelsheim, Mark; Esko, Tõnu; Brundel, Bianca J J M; Peal, David S; Evans, David M; Nolte, Ilja M; Segrè, Ayellet V; Holm, Hilma; Handsaker, Robert E; Westra, Harm-Jan; Johnson, Toby; Isaacs, Aaron; Yang, Jian; Lundby, Alicia; Zhao, Jing Hua; Kim, Young Jin; Go, Min Jin; Almgren, Peter; Bochud, Murielle; Boucher, Gabrielle; Cornelis, Marilyn C; Gudbjartsson, Daniel; Hadley, David; Van Der Harst, Pim; Hayward, Caroline; Heijer, Martin Den; Igl, Wilmar; Jackson, Anne U; Kutalik, Zoltán; Luan, Jian’an; Kemp, John P; Kristiansson, Kati; Ladenvall, Claes; Lorentzon, Mattias; Montasser, May E; Njajou, Omer T; O’Reilly, Paul F; Padmanabhan, Sandosh; Pourcain, Beate St.; Rankinen, Tuomo; Salo, Perttu; Tanaka, Toshiko; Timpson, Nicholas J; Vitart, Veronique; Waite, Lindsay; Wheeler, William; Zhang, Weihua; Draisma, Harmen H M; Feitosa, Mary F; Kerr, Kathleen F; Lind, Penelope A; Mihailov, Evelin; Onland-Moret, N Charlotte; Song, Ci; Weedon, Michael N; Xie, Weijia; Yengo, Loic; Absher, Devin; Albert, Christine M; Alonso, Alvaro; Arking, Dan E; de Bakker, Paul I W; Balkau, Beverley; Barlassina, Cristina; Benaglio, Paola; Bis, Joshua C; Bouatia-Naji, Nabila; Brage, Søren; Chanock, Stephen J; Chines, Peter S; Chung, Mina; Darbar, Dawood; Dina, Christian; Dörr, Marcus; Elliott, Paul; Felix, Stephan B; Fischer, Krista; Fuchsberger, Christian; de Geus, Eco J C; Goyette, Philippe; Gudnason, Vilmundur; Harris, Tamara B; Hartikainen, Anna-liisa; Havulinna, Aki S; Heckbert, Susan R; Hicks, Andrew A; Hofman, Albert; Holewijn, Suzanne; Hoogstra-Berends, Femke; Hottenga, Jouke-Jan; Jensen, Majken K; Johansson, Åsa; Junttila, Juhani; Kääb, Stefan; Kanon, Bart; Ketkar, Shamika; Khaw, Kay-Tee; Knowles, Joshua W; Kooner, Angrad S; Kors, Jan A; Kumari, Meena; Milani, Lili; Laiho, Päivi; Lakatta, Edward G; Langenberg, Claudia; Leusink, Maarten; Liu, Yongmei; Luben, Robert N; Lunetta, Kathryn L; Lynch, Stacey N; Markus, Marcello R P; Marques-Vidal, Pedro; Leach, Irene Mateo; McArdle, Wendy L; McCarroll, Steven A; Medland, Sarah E; Miller, Kathryn A; Montgomery, Grant W; Morrison, Alanna C; Müller-Nurasyid, Martina; Navarro, Pau; Nelis, Mari; O’Connell, Jeffrey R; O’Donnell, Christopher J; Ong, Ken K; Newman, Anne B; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P; Psaty, Bruce M; Rao, Dabeeru C; Ring, Susan M; Rossin, Elizabeth J; Rudan, Diana; Sanna, Serena; Scott, Robert A; Sehmi, Jaban S; Sharp, Stephen; Shin, Jordan T; Singleton, Andrew B; Smith, Albert V; Soranzo, Nicole; Spector, Tim D; Stewart, Chip; Stringham, Heather M; Tarasov, Kirill V; Uitterlinden, André G; Vandenput, Liesbeth; Hwang, Shih-Jen; Whitfield, John B; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilson, James F; Witteman, Jacqueline C M; Wong, Andrew; Wong, Quenna; Jamshidi, Yalda; Zitting, Paavo; Boer, Jolanda M A; Boomsma, Dorret I; Borecki, Ingrid B; Van Duijn, Cornelia M; Ekelund, Ulf; Forouhi, Nita G; Froguel, Philippe; Hingorani, Aroon; Ingelsson, Erik; Kivimaki, Mika; Kronmal, Richard A; Kuh, Diana; Lind, Lars; Martin, Nicholas G; Oostra, Ben A; Pedersen, Nancy L; Quertermous, Thomas; Rotter, Jerome I; van der Schouw, Yvonne T; Verschuren, W M Monique; Walker, Mark; Albanes, Demetrius; Arnar, David O; Assimes, Themistocles L; Bandinelli, Stefania; Boehnke, Michael; de Boer, Rudolf A; Bouchard, Claude; Caulfield, W L Mark; Chambers, John C; Curhan, Gary; Cusi, Daniele; Eriksson, Johan; Ferrucci, Luigi; van Gilst, Wiek H; Glorioso, Nicola; de Graaf, Jacqueline; Groop, Leif; Gyllensten, Ulf; Hsueh, Wen-Chi; Hu, Frank B; Huikuri, Heikki V; Hunter, David J; Iribarren, Carlos; Isomaa, Bo; Jarvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kiemeney, Lambertus A; van der Klauw, Melanie M; Kooner, Jaspal S; Kraft, Peter; Iacoviello, Licia; Lehtimäki, Terho; Lokki, Marja-Liisa L; Mitchell, Braxton D; Navis, Gerjan; Nieminen, Markku S; Ohlsson, Claes; Poulter, Neil R; Qi, Lu; Raitakari, Olli T; Rimm, Eric B; Rioux, John D; Rizzi, Federica; Rudan, Igor; Salomaa, Veikko; Sever, Peter S; Shields, Denis C; Shuldiner, Alan R; Sinisalo, Juha; Stanton, Alice V; Stolk, Ronald P; Strachan, David P; Tardif, Jean-Claude; Thorsteinsdottir, Unnur; Tuomilehto, Jaako; van Veldhuisen, Dirk J; Virtamo, Jarmo; Viikari, Jorma; Vollenweider, Peter; Waeber, Gérard; Widen, Elisabeth; Cho, Yoon Shin; Olsen, Jesper V; Visscher, Peter M; Willer, Cristen; Franke, Lude; Erdmann, Jeanette; Thompson, John R; Pfeufer, Arne; Sotoodehnia, Nona; Newton-Cheh, Christopher; Ellinor, Patrick T; Stricker, Bruno H Ch; Metspalu, Andres; Perola, Markus; Beckmann, Jacques S; Smith, George Davey; Stefansson, Kari; Wareham, Nicholas J; Munroe, Patricia B; Sibon, Ody C M; Milan, David J; Snieder, Harold; Samani, Nilesh J; Loos, Ruth J F

2013-01-01

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate–increasing and heart rate–decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. PMID:23583979

Baroreflex Activation Therapy in Congestive Heart Failure: Novel Findings and Future Insights.

PubMed

Grassi, Guido; Brambilla, GianMaria; Pizzalla, Daniela Prata; Seravalle, Gino

2016-08-01

Congestive heart failure is characterized by hemodynamic and non-hemodynamic abnormalities, the latter including an activation of the sympathetic influences to the heart and peripheral circulation coupled with an impairment of baroreceptor control of autonomic function. Evidence has been provided that both these alterations are hallmark features of the disease with a specific relevance for the disease progression as well as for the development of life-threatening cardiac arrhythmias. In addition, a number of studies have documented in heart failure the adverse prognostic role of the sympathetic and baroreflex alterations, which both are regarded as major independent determinants of cardiovascular morbidity and mortality. This represents the pathophysiological and clinical background for the use of carotid baroreceptor activation therapy in the treatment of congestive heart failure. Promising data collected in experimental animal models of heart failure have supported the recent performance of pilot small-scale clinical studies, aimed at providing initial information in this area. The results of these studies demonstrated the clinical safety and efficacy of the intervention which has been tested in large-scale clinical studies. The present paper will critically review the background and main results of the published studies designed at defining the clinical impact of baroreflex activation therapy in congestive heart failure patients. Emphasis will be given to the strengths and limitations of such studies, which represent the background for the ongoing clinical trials testing the long-term effects of the device in heart failure patients.

Prevalence and associated factors for decreased appetite among patients with stable heart failure.

PubMed

Andreae, Christina; Strömberg, Anna; Årestedt, Kristofer

2016-06-01

To explore the prevalence of decreased appetite and factors associated with appetite among patients with stable heart failure. Decreased appetite is an important factor for the development of undernutrition among patients with heart failure, but there are knowledge gaps about prevalence and the factors related to appetite in this patient group. Observational, cross-sectional study. A total of 186 patients with mild to severe heart failure were consecutively recruited from three heart failure outpatient clinics. Data were obtained from medical records (heart failure diagnosis, comorbidity and medical treatment) and self-rated questionnaires (demographics, appetite, self-perceived health, symptoms of depression and sleep). Blood samples were taken to determine myocardial stress and nutrition status. Heart failure symptoms and cognitive function were assessed by clinical examinations. The Council on Nutrition Appetite Questionnaire was used to assess self-reported appetite. Bivariate correlations and multivariate linear regression analyses were conducted to explore factors associated with appetite. Seventy-one patients (38%) experienced a loss of appetite with a significant risk of developing weight loss. The final multiple regression model showed that age, symptoms of depression, insomnia, cognitive function and pharmacological treatment were associated with appetite, explaining 27% of the total variance. In this cross-sectional study, a large share of patients with heart failure was affected by decreased appetite, associated with demographic, psychosocial and medical factors. Loss of appetite is a prevalent problem among patients with heart failure that may lead to undernutrition. Health care professionals should routinely assess appetite and discuss patients' experiences of appetite, nutrition intake and body weight and give appropriate nutritional advice with respect to individual needs. © 2016 John Wiley & Sons Ltd.

Endothelin-1 signalling controls early embryonic heart rate in vitro and in vivo.

PubMed

Karppinen, S; Rapila, R; Mäkikallio, K; Hänninen, S L; Rysä, J; Vuolteenaho, O; Tavi, P

2014-02-01

Spontaneous activity of embryonic cardiomyocytes originates from sarcoplasmic reticulum (SR) Ca(2+) release during early cardiogenesis. However, the regulation of heart rate during embryonic development is still not clear. The aim of this study was to determine how endothelin-1 (ET-1) affects the heart rate of embryonic mice, as well as the pathway through which it exerts its effects. The effects of ET-1 and ET-1 receptor inhibition on cardiac contraction were studied using confocal Ca(2+) imaging of isolated mouse embryonic ventricular cardiomyocytes and ultrasonographic examination of embryonic cardiac contractions in utero. In addition, the amount of ET-1 peptide and ET receptor a (ETa) and b (ETb) mRNA levels were measured during different stages of development of the cardiac muscle. High ET-1 concentration and expression of both ETa and ETb receptors was observed in early cardiac tissue. ET-1 was found to increase the frequency of spontaneous Ca(2+) oscillations in E10.5 embryonic cardiomyocytes in vitro. Non-specific inhibition of ET receptors with tezosentan caused arrhythmia and bradycardia in isolated embryonic cardiomyocytes and in whole embryonic hearts both in vitro (E10.5) and in utero (E12.5). ET-1-mediated stimulation of early heart rate was found to occur via ETb receptors and subsequent inositol trisphosphate receptor activation and increased SR Ca(2+) leak. Endothelin-1 is required to maintain a sufficient heart rate, as well as to prevent arrhythmia during early development of the mouse heart. This is achieved through ETb receptor, which stimulates Ca(2+) leak through IP3 receptors. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Ventricular conduction and long-term heart failure outcomes and mortality in African Americans: insights from the Jackson Heart Study.

PubMed

Mentz, Robert J; Greiner, Melissa A; DeVore, Adam D; Dunlay, Shannon M; Choudhary, Gaurav; Ahmad, Tariq; Khazanie, Prateeti; Randolph, Tiffany C; Griswold, Michael E; Eapen, Zubin J; O'Brien, Emily C; Thomas, Kevin L; Curtis, Lesley H; Hernandez, Adrian F

2015-03-01

QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities. © 2015 American Heart Association, Inc.

Higher Heart Failure Risk Seen in Some Cancers

Cancer.gov

Some people treated for breast cancer or lymphoma have a higher risk of developing congestive heart failure than people who haven’t had cancer, a new study shows. As this Cancer Currents blog post reports, the risk persisted for at least 20 years.

Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study.

PubMed

Lebwohl, Benjamin; Cao, Yin; Zong, Geng; Hu, Frank B; Green, Peter H R; Neugut, Alfred I; Rimm, Eric B; Sampson, Laura; Dougherty, Lauren W; Giovannucci, Edward; Willett, Walter C; Sun, Qi; Chan, Andrew T

2017-05-02

Objective  To examine the association of long term intake of gluten with the development of incident coronary heart disease. Design  Prospective cohort study. Setting and participants  64 714 women in the Nurses' Health Study and 45 303 men in the Health Professionals Follow-up Study without a history of coronary heart disease who completed a 131 item semiquantitative food frequency questionnaire in 1986 that was updated every four years through 2010. Exposure  Consumption of gluten, estimated from food frequency questionnaires. Main outcome measure  Development of coronary heart disease (fatal or non-fatal myocardial infarction). Results  During 26 years of follow-up encompassing 2 273 931 person years, 2431 women and 4098 men developed coronary heart disease. Compared with participants in the lowest fifth of gluten intake, who had a coronary heart disease incidence rate of 352 per 100 000 person years, those in the highest fifth had a rate of 277 events per 100 000 person years, leading to an unadjusted rate difference of 75 (95% confidence interval 51 to 98) fewer cases of coronary heart disease per 100 000 person years. After adjustment for known risk factors, participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0.95 (95% confidence interval 0.88 to 1.02; P for trend=0.29). After additional adjustment for intake of whole grains (leaving the remaining variance of gluten corresponding to refined grains), the multivariate hazard ratio was 1.00 (0.92 to 1.09; P for trend=0.77). In contrast, after additional adjustment for intake of refined grains (leaving the variance of gluten intake correlating with whole grain intake), estimated gluten consumption was associated with a lower risk of coronary heart disease (multivariate hazard ratio 0.85, 0.77 to 0.93; P for trend=0.002). Conclusion  Long term dietary intake of gluten was not associated with risk of coronary heart disease. However, the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten-free diets among people without celiac disease should not be encouraged. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001.

PubMed

Louis, A; Cleland, J G; Crabbe, S; Ford, S; Thackray, S; Houghton, T; Clark, A

2001-06-01

This is a synopsis of presentations made at the American College of Cardiology (ACC) in 2001 summarising recent research developments relating to heart failure. Clinical studies of particular interest to physicians with an interest in heart failure and its prevention are reviewed. The COPERNICUS trial lends further support to the use of the beta-blocker, carvedilol, in severe heart failure and the CAPRICORN trial to its use in patients with post-infarction left ventricular systolic dysfunction. The MIRACLE study reinforces the evidence from three smaller trials that cardiac resynchronisation therapy is an effective treatment for the relief of symptoms in patients with severe heart failure and cardiac dyssynchrony. The STAF trial casts further doubt on the wisdom of cardioversion as a routine strategy for the management of chronic atrial fibrillation. The RITZ-2 trial suggests that an intravenous, non-selective endothelin antagonist is effective in improving haemodynamics and symptoms and possibly in reducing morbidity in severe heart failure. Observational studies in heart failure suggest that a moderate excess of body fat and elevated blood cholesterol may be desirable in patients with heart failure, challenging the current non-evidenced-based vogue for cholesterol lowering therapy in heart failure. The RENAISSANCE and RECOVER outcome studies of etanercept, a tumour necrosis factor (TNF) receptor analogue that blocks the effect of TNF, were stopped because of lack of evidence of benefit shortly after the ACC.

Development and pilot testing of a disease management program for low literacy patients with heart failure.

PubMed

DeWalt, Darren A; Pignone, Michael; Malone, Robb; Rawls, Cathy; Kosnar, Margaret C; George, Geeta; Bryant, Betsy; Rothman, Russell L; Angel, Bonnie

2004-10-01

Development and pilot testing of a disease management program for low literacy patients with heart failure. Randomized trials have shown that disease management programs can reduce hospitalizations and improve symptoms for patients with congestive heart failure. We sought to create and pilot test such a program for patients with low literacy skills. We used focus groups and individual cognitive response interviews (CRIs) to develop an educational booklet for low literacy patients with heart failure. We incorporated the booklet into a disease management intervention that also included an initial individualized 1-h educational session and scheduled supportive phone calls that were tapered over 6 weeks. We then conducted a 3-month before-after study on patients with low literacy skills (<9th grade literacy level) in a university internal medicine clinic to test the acceptability and efficacy of our program. Outcomes of interest included heart failure-related knowledge, self-care behavior and heart failure-related symptoms measured on the Minnesota Living with Heart Failure (MLwHF) scale. Twenty-five patients were enrolled and 23 (92%) completed 3-month follow-up. Mean age was 60 years (range 35-74), 60% were men, 60% were African-American, and 74% had household income under $15,000 per year. The median reading level was fifth grade with 32% reading at or below the third grade level. Mean knowledge score at baseline was 67% and did not improve after the intervention. The proportion of patients reporting weighing themselves daily increased from 32% at baseline to 100% at 12 weeks. Mean improvement on the MLwHF scale was 9.9 points over the 3-month trial (95% CI: 0.5, 19.2), which corresponds to an improvement in one class on the New York Heart Association heart failure scale. A heart failure disease management program designed specifically for patients with low literacy skills is acceptable and is associated with improvement in self-care behavior and heart failure related symptoms.

SenseMyHeart: A cloud service and API for wearable heart monitors.

PubMed

Pinto Silva, P M; Silva Cunha, J P

2015-01-01

In the era of ubiquitous computing, the growing adoption of wearable systems and body sensor networks is trailing the path for new research and software for cardiovascular intensity, energy expenditure and stress and fatigue detection through cardiovascular monitoring. Several systems have received clinical-certification and provide huge amounts of reliable heart-related data in a continuous basis. PhysioNet provides equally reliable open-source software tools for ECG processing and analysis that can be combined with these devices. However, this software remains difficult to use in a mobile environment and for researchers unfamiliar with Linux-based systems. In the present paper we present an approach that aims at tackling these limitations by developing a cloud service that provides an API for a PhysioNet-based pipeline for ECG processing and Heart Rate Variability measurement. We describe the proposed solution, along with its advantages and tradeoffs. We also present some client tools (windows and Android) and several projects where the developed cloud service has been used successfully as a standard for Heart Rate and Heart Rate Variability studies in different scenarios.

Strategies for Analyzing Cardiac Phenotypes in the Zebrafish Embryo

PubMed Central

Houk, Andrew R.; Yelon, Deborah

2017-01-01

The molecular mechanisms underlying cardiogenesis are of critical biomedical importance due to the high prevalence of cardiac birth defects. Over the past two decades, the zebrafish has served as a powerful model organism for investigating heart development, facilitated by its powerful combination of optical access to the embryonic heart and plentiful opportunities for genetic analysis. Work in zebrafish has identified numerous factors that are required for various aspects of heart formation, including the specification and differentiation of cardiac progenitor cells, the morphogenesis of the heart tube, cardiac chambers, and atrioventricular canal, and the establishment of proper cardiac function. However, our current roster of regulators of cardiogenesis is by no means complete. It is therefore valuable for ongoing studies to continue pursuit of additional genes and pathways that control the size, shape, and function of the zebrafish heart. An extensive arsenal of techniques is available to distinguish whether particular mutations, morpholinos, or small molecules disrupt specific processes during heart development. In this chapter, we provide a guide to the experimental strategies that are especially effective for the characterization of cardiac phenotypes in the zebrafish embryo. PMID:27312497

Initial Field Test of a Cloud-Based Cardiac Auscultation System to Determine Murmur Etiology in Rural China.

PubMed

Pyles, Lee; Hemmati, Pouya; Pan, J; Yu, Xiaoju; Liu, Ke; Wang, Jing; Tsakistos, Andreas; Zheleva, Bistra; Shao, Weiguang; Ni, Quan

2017-04-01

A system for collection, distribution, and long distant, asynchronous interpretation of cardiac auscultation has been developed and field-tested in rural China. We initiated a proof-of-concept test as a critical component of design of a system to allow rural physicians with little experience in evaluation of congenital heart disease (CHD) to obtain assistance in diagnosis and management of children with significant heart disease. The project tested the hypothesis that acceptable screening of heart murmurs could be accomplished using a digital stethoscope and internet cloud transmittal to deliver phonocardiograms to an experienced observer. Of the 7993 children who underwent school-based screening in the Menghai District of Yunnan Province, Peoples Republic of China, 149 had a murmur noted by a screener. They had digital heart sounds and phonocardiograms collected with the HeartLink tele auscultation system, and underwent echocardiography by a cardiology resident from the First Affiliated Hospital of Kunming Medical University. The digital phonocardiograms, stored on a cloud server, were later remotely reviewed by a board-certified American pediatric cardiologist. Fourteen of these subjects were found to have CHD confirmed by echocardiogram. Using the HeartLink system, the pediatric cardiologist identified 11 of the 14 subjects with pathological murmurs, and missed three subjects with atrial septal defects, which were incorrectly identified as venous hum or Still's murmur. In addition, ten subjects were recorded as having pathological murmurs, when no CHD was confirmed by echocardiography during the field study. The overall test accuracy was 91% with 78.5% sensitivity and 92.6% specificity. This proof-of-concept study demonstrated the feasibility of differentiating pathologic murmurs due to CHD from normal functional heart murmurs with the HeartLink system. This field study is an initial step to develop a cost-effective CHD screening strategy in low-resource settings with a shortage of trained medical professionals and pediatric heart programs.

Overlapping and Opposing Functions of G Protein-coupled Receptor Kinase 2 (GRK2) and GRK5 during Heart Development*

PubMed Central

Philipp, Melanie; Berger, Ina M.; Just, Steffen; Caron, Marc G.

2014-01-01

G protein-coupled receptor kinases 2 (GRK2) and 5 (GRK5) are fundamental regulators of cardiac performance in adults but are less well characterized for their function in the hearts of embryos. GRK2 and -5 belong to different subfamilies and function as competitors in the control of certain receptors and signaling pathways. In this study, we used zebrafish to investigate whether the fish homologs of GRK2 and -5, Grk2/3 and Grk5, also have unique, complementary, or competitive roles during heart development. We found that they differentially regulate the heart rate of early embryos and equally facilitate heart function in older embryos and that both are required to develop proper cardiac morphology. A loss of Grk2/3 results in dilated atria and hypoplastic ventricles, and the hearts of embryos depleted in Grk5 present with a generalized atrophy. This Grk5 morphant phenotype was associated with an overall decrease of early cardiac progenitors as well as a reduction in the area occupied by myocardial progenitor cells. In the case of Grk2/3, the progenitor decrease was confined to a subset of precursor cells with a committed ventricular fate. We attempted to rescue the GRK loss-of-function heart phenotypes by downstream activation of Hedgehog signaling. The Grk2/3 loss-of-function embryos were rescued by this approach, but Grk5 embryos failed to respond. In summary, we found that GRK2 and GRK5 control cardiac function as well as morphogenesis during development although with different morphological outcomes. PMID:25104355

Economic impact of heart failure according to the effects of kidney failure.

PubMed

Sicras Mainar, Antoni; Navarro Artieda, Ruth; Ibáñez Nolla, Jordi

2015-01-01

To evaluate the use of health care resources and their cost according to the effects of kidney failure in heart failure patients during 2-year follow-up in a population setting. Observational retrospective study based on a review of medical records. The study included patients ≥ 45 years treated for heart failure from 2008 to 2010. The patients were divided into 2 groups according to the presence/absence of KF. Main outcome variables were comorbidity, clinical status (functional class, etiology), metabolic syndrome, costs, and new cases of cardiovascular events and kidney failure. The cost model included direct and indirect health care costs. Statistical analysis included multiple regression models. The study recruited 1600 patients (prevalence, 4.0%; mean age 72.4 years; women, 59.7%). Of these patients, 70.1% had hypertension, 47.1% had dyslipidemia, and 36.2% had diabetes mellitus. We analyzed 433 patients (27.1%) with kidney failure and 1167 (72.9%) without kidney failure. Patients with kidney failure were associated with functional class III-IV (54.1% vs 40.8%) and metabolic syndrome (65.3% vs 51.9%, P<.01). The average unit cost was €10,711.40. The corrected cost in the presence of kidney failure was €14,868.20 vs €9,364.50 (P=.001). During follow-up, 11.7% patients developed ischemic heart disease, 18.8% developed kidney failure, and 36.1% developed heart failure exacerbation. Comorbidity associated with heart failure is high. The presence of kidney failure increases the use of health resources and leads to higher costs within the National Health System. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

A genome resource to address mechanisms of developmental programming: determination of the fetal sheep heart transcriptome.

PubMed

Cox, Laura A; Glenn, Jeremy P; Spradling, Kimberly D; Nijland, Mark J; Garcia, Roy; Nathanielsz, Peter W; Ford, Stephen P

2012-06-15

The pregnant sheep has provided seminal insights into reproduction related to animal and human development (ovarian function, fertility, implantation, fetal growth, parturition and lactation). Fetal sheep physiology has been extensively studied since 1950, contributing significantly to the basis for our understanding of many aspects of fetal development and behaviour that remain in use in clinical practice today. Understanding mechanisms requires the combination of systems approaches uniquely available in fetal sheep with the power of genomic studies. Absence of the full range of sheep genomic resources has limited the full realization of the power of this model, impeding progress in emerging areas of pregnancy biology such as developmental programming. We have examined the expressed fetal sheep heart transcriptome using high-throughput sequencing technologies. In so doing we identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. Genes with the highest expression levels and with novel exons in the fetal heart transcriptome are known to play central roles in muscle development. We show that high-throughput sequencing methods can generate extensive transcriptome information in the absence of an assembled and annotated genome for that species. The gene sequence data obtained provide a unique genomic resource for sheep specific genetic technology development and, combined with the polymorphism data, augment annotation and assembly of the sheep genome. In addition, identification and pathway analysis of novel fetal sheep heart transcriptome splice variants is a first step towards revealing mechanisms of genetic variation and gene environment interactions during fetal heart development.

Junctional ectopic tachycardia after infant heart surgery: incidence and outcomes.

PubMed

Zampi, Jeffrey D; Hirsch, Jennifer C; Gurney, James G; Donohue, Janet E; Yu, Sunkyung; LaPage, Martin J; Hanauer, David A; Charpie, John R

2012-12-01

Junctional ectopic tachycardia (JET) is an arrhythmia observed almost exclusively after open heart surgery in children. Current literature on JET has not focused on patients at the highest risk of both developing and being negatively impacted by JET. The purpose of this study was to determine the overall incidence of JET in an infant patient cohort undergoing open cardiac surgery, to identify patient- and procedure-related factors associated with developing JET, and to assess the clinical impact of JET on patient outcomes. We performed a nested case-control study from the complete cohort of patients at our institution younger than 1 year of age who underwent open heart surgery between 2005 and 2010. JET patients were compared with an age matched control group undergoing open heart surgery without JET regarding potential risk factors and outcomes. The overall incidence of JET in infants after open cardiac surgery was 14.3 %. From multivariate analyses, complete repair of tetralogy of Fallot [adjusted odds ratio (AOR) 2.0, 95 % CI 1.12-3.57] and longer aortic cross clamp times (AOR 1.02, 95 % CI 1.01-1.03) increased the risk of developing JET. Patients with JET had longer length of intubation, intensive care unit stays, and total length of hospitalization, and were more likely to require extracorporeal membrane oxygenation support (13 vs. 4.3 %). JET is a common postoperative arrhythmia in infants after open heart operations. Both anatomic substrate and surgical procedure contribute to the overall risk of developing JET. Developing JET is associated with worse clinical outcomes.

A genome resource to address mechanisms of developmental programming: determination of the fetal sheep heart transcriptome

PubMed Central

Cox, Laura A; Glenn, Jeremy P; Spradling, Kimberly D; Nijland, Mark J; Garcia, Roy; Nathanielsz, Peter W; Ford, Stephen P

2012-01-01

The pregnant sheep has provided seminal insights into reproduction related to animal and human development (ovarian function, fertility, implantation, fetal growth, parturition and lactation). Fetal sheep physiology has been extensively studied since 1950, contributing significantly to the basis for our understanding of many aspects of fetal development and behaviour that remain in use in clinical practice today. Understanding mechanisms requires the combination of systems approaches uniquely available in fetal sheep with the power of genomic studies. Absence of the full range of sheep genomic resources has limited the full realization of the power of this model, impeding progress in emerging areas of pregnancy biology such as developmental programming. We have examined the expressed fetal sheep heart transcriptome using high-throughput sequencing technologies. In so doing we identified 36,737 novel transcripts and describe genes, gene variants and pathways relevant to fundamental developmental mechanisms. Genes with the highest expression levels and with novel exons in the fetal heart transcriptome are known to play central roles in muscle development. We show that high-throughput sequencing methods can generate extensive transcriptome information in the absence of an assembled and annotated genome for that species. The gene sequence data obtained provide a unique genomic resource for sheep specific genetic technology development and, combined with the polymorphism data, augment annotation and assembly of the sheep genome. In addition, identification and pathway analysis of novel fetal sheep heart transcriptome splice variants is a first step towards revealing mechanisms of genetic variation and gene environment interactions during fetal heart development. PMID:22508961

Mitogen-Activated Protein Kinase Signaling in the Heart: Angels Versus Demons in a Heart-Breaking Tale

PubMed Central

ROSE, BETH A.; FORCE, THOMAS; WANG, YIBIN

2013-01-01

Among the myriad of intra-cellular signaling networks that govern the cardiac development and pathogenesis, mitogen-activated protein kinases (MAPKs) are prominent players that have been the focus of extensive investigations in the past decades. The four best characterized MAPK subfamilies, ERK1/2, JNK, p38, and ERK5, are the targets of pharmacological and genetic manipulations to uncover their roles in cardiac development, function, and diseases. However, information reported in the literature from these efforts has not yet resulted in a clear view about the roles of specific MAPK pathways in heart. Rather, controversies from contradictive results have led to a perception that MAPKs are ambiguous characters in heart with both protective and detrimental effects. The primary object of this review is to provide a comprehensive overview of the current progress, in an effort to highlight the areas where consensus is established verses the ones where controversy remains. MAPKs in cardiac development, cardiac hypertrophy, ischemia/reperfusion injury, and pathological remodeling are the main focuses of this review as these represent the most critical issues for evaluating MAPKs as viable targets of therapeutic development. The studies presented in this review will help to reveal the major challenges in the field and the limitations of current approaches and point to a critical need in future studies to gain better understanding of the fundamental mechanisms of MAPK function and regulation in the heart. PMID:20959622

Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice

DOE PAGES

Yuan, Chen-Ching; Muthu, Priya; Kazmierczak, Katarzyna; ...

2015-06-29

Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 →Valine) mutation-induced changes in heart morphology and function coincided with largely reduced RLC phosphorylation in situ. In this paper, we hypothesized that the introduction of a constitutively phosphorylated Serine15 (S15D) into the hearts of D166V mice would prevent the development of a deleterious HCM phenotype. In supportmore » of this notion, MLCK-induced phosphorylation of D166V-mutated hearts was found to rescue some of their abnormal contractile properties. Tg-S15D-D166V mice were generated with the human cardiac RLC-S15D-D166V construct substituted for mouse cardiac RLC and were subjected to functional, structural, and morphological assessments. The results were compared with Tg-WT and Tg-D166V mice expressing the human ventricular RLC-WT or its D166V mutant, respectively. Echocardiography and invasive hemodynamic studies demonstrated significant improvements of intact heart function in S15D-D166V mice compared with D166V, with the systolic and diastolic indices reaching those monitored in WT mice. A largely reduced maximal tension and abnormally high myofilament Ca 2+ sensitivity observed in D166V-mutated hearts were reversed in S15D-D166V mice. Low-angle X-ray diffraction study revealed that altered myofilament structures present in HCM-D166V mice were mitigated in S15D-D166V rescue mice. Finally, our collective results suggest that expression of pseudophosphorylated RLC in the hearts of HCM mice is sufficient to prevent the development of the pathological HCM phenotype.« less

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.

Pulmonary Microwave Ablation Near the Heart: Antenna Positioning Can Mitigate Cardiac Complications in a Porcine Model

PubMed Central

Nocerino, Elisabetta; Mason, Peter J.; Schwahn, Denise J.; Hetzel, Scott; Turnquist, Alyssa M.; Lee, Fred T.; Brace, Christopher L.

2017-01-01

Purpose To determine how close to the heart pulmonary microwave ablation can be performed without causing cardiac tissue injury or significant arrhythmia. Materials and Methods The study was performed with approval from the institutional animal care and use committee. Computed tomographic fluoroscopically guided microwave ablation of the lung was performed in 12 swine. Antennas were randomized to either parallel (180° ± 20°) or perpendicular (90° ± 20°) orientation relative to the heart surface and to distances of 0–10 mm from the heart. Ablations were performed at 65 W for 5 minutes or until a significant arrhythmia (asystole, heart block, bradycardia, supraventricular or ventricular tachycardia) developed. Heart tissue was evaluated with vital staining and histologic examination. Data were analyzed with mixed effects logistic regression, receiver operating characteristic curves, and the Fisher exact test. Results Thirty-four pulmonary microwave ablations were performed with the antenna a median distance of 4 mm from the heart in both perpendicular (n = 17) and parallel (n = 17) orientation. Significant arrhythmias developed during six (18%) ablations. Cardiac tissue injury occurred with 17 ablations (50%). Risk of arrhythmia and tissue injury decreased with increasing antenna distance from the heart with both antenna orientations. No cardiac complication occurred with a distance of greater than or equal to 4.4 mm from the heart. The ablation zone extended to the pleural surface adjacent to the heart in 71% of parallel and 17% of perpendicular ablations performed 5–10 mm from the heart. Conclusion Microwave lung ablations performed more than or equal to 5 mm from the heart were associated with a low risk of cardiac complications. © RSNA, 2016 PMID:27732159

Design of the heart failure endpoint evaluation of AII-antagonist losartan (HEAAL) study in patients intolerant to ACE-inhibitor.

PubMed

Konstam, Marvin A; Poole-Wilson, Philip A; Dickstein, Kenneth; Drexler, Helmut; Justice, Steven J; Komajda, Michel; Malbecq, William; Martinez, Felipe A; Neaton, James D; Riegger, Gunter A J; Guptha, Soneil

2008-09-01

In patients with heart failure and reduced left ventricular ejection fraction, angiotensin receptor blockers have been found to reduce mortality and morbidity and to prevent or reverse left ventricular remodelling, compared to optimized background treatment. In light of these data, The Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL) study was developed to determine whether losartan 150 mg is superior to losartan 50 mg (antihypertensive dose) in reducing morbidity and mortality among patients with symptomatic heart failure who are intolerant of angiotensin-converting enzyme (ACE)-inhibitors. To compare the effect of high and moderate doses of losartan on the primary endpoint of all-cause mortality and hospitalisation due to heart failure in patients (n = 3834) with symptomatic heart failure and an ejection fraction < or = 40% who are intolerant of ACE-inhibitor treatment. This paper presents the rationale, trial design, and baseline characteristics of the study population. The study, which completed recruitment on 31 March 2005, is event-driven and is estimated to accrue the target of 1710 adjudicated primary events during the latter half of 2008. The results of HEAAL should facilitate selection of an optimal dosing regimen for losartan in patients with symptomatic heart failure who are intolerant of ACE-inhibitors.

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.

Models of torsades de pointes: effects of FPL64176, DPI201106, dofetilide, and chromanol 293B in isolated rabbit and guinea pig hearts.

PubMed

Cheng, Hsien C; Incardona, Josephine

2009-01-01

For studying the torsades de pointes (TdP) liability of a compound, most high and medium throughput methods use surrogate markers such as HERG inhibition and QT prolongation. In this study, we have tested whether isolated hearts may be modified to allow TdP to be the direct readout. Isolated spontaneously beating rabbit and guinea pig hearts were perfused according to the Langendorff method in hypokalemic (2.1 mM) solution. The in vitro lead II ECG equivalent and the incidence of TdP were monitored for 1 h. In addition, heart rate, QTc, Tp-Te, short-term variability (STV), time to arrhythmia, and time to TdP were also analyzed. FPL64176, a calcium channel activator; and DPI201106, a sodium channel inactivation inhibitor, produced TdP in isolated rabbit and guinea pig hearts in a concentration dependent manner; guinea pig hearts were 3- to 5-fold more sensitive than rabbit hearts. Both compounds also increased QTc and STV. In contrast, dofetilide, an IKr inhibitor, produced no (or a low incidence of) TdP in both species, in spite of prolongation of QTc intervals. Chromanol 293B, an IKs inhibitor, did not produce TdP in rabbit hearts but elicited TdP concentration dependently in guinea pig hearts even though the compound had no effect on QTc intervals. IKs inhibition appears to be more likely to produce TdP in isolated guinea pig hearts than IKr inhibition. Chromanol 293B did not produce TdP in rabbit hearts presumably due to a low level of IKs channels in the heart. TdP produced in this study was consistent with the notion that its production was a consequence of reduced repolarization reserve, thereby causing rhythmic abnormalities. This isolated, perfused, and spontaneously beating rabbit and guinea pig heart preparation in hypokalemic medium may be useful as a preclinical test model for studying proarrhythmic liability of compounds in new drug development.

Dioxin inhibition of swim bladder development in zebrafish: is it secondary to heart failure?

PubMed

Yue, Monica S; Peterson, Richard E; Heideman, Warren

2015-05-01

The swim bladder is a gas-filled organ that is used for regulating buoyancy and is essential for survival in most teleost species. In zebrafish, swim bladder development begins during embryogenesis and inflation occurs within 5 days post fertilization (dpf). Embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) before 96 h post fertilization (hpf) developed swim bladders normally until the growth/elongation phase, at which point growth was arrested. It is known that TCDD exposure causes heart malformations that lead to heart failure in zebrafish larvae, and that blood circulation is a key factor in normal development of the swim bladder. The adverse effects of TCDD exposure on the heart occur during the same period of time that swim bladder development and growth occurs. Based on this coincident timing, and the dependence of swim bladder development on proper circulatory development, we hypothesized that the adverse effects of TCDD on swim bladder development were secondary to heart failure. We compared swim bladder development in TCDD-exposed embryos to: (1) silent heart morphants, which lack cardiac contractility, and (2) transiently transgenic cmlc2:caAHR-2AtRFP embryos, which mimic TCDD-induced heart failure via heart-specific, constitutive activation of AHR signaling. Both of these treatment groups, which were not exposed to TCDD, developed hypoplastic swim bladders of comparable size and morphology to those found in TCDD-exposed embryos. Furthermore, in all treatment groups swim bladder development was arrested during the growth/elongation phase. Together, these findings support a potential role for heart failure in the inhibition of swim bladder development caused by TCDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and heart failure.

PubMed

Jordan, Jens; Toplak, Hermann; Grassi, Guido; Yumuk, Volkan; Kotsis, Vasilios; Engeli, Stefan; Cuspidi, Cesare; Nilsson, Peter M; Finer, Nick; Doehner, Wolfram

2016-09-01

Obese individuals are more likely to develop heart failure. Yet, once heart failure is established, the impact of overweight and obesity on prognosis and survival is unclear. The purpose of this joint scientific statement of the European Association for the Study of Obesity and the European Society of Hypertension is to provide an overview on the current scientific literature on obesity and heart failure in terms of prognosis, mechanisms, and clinical management implications. Moreover, the document identifies open questions that ought to be addressed. The need for more tailored weight management recommendations in heart failure will be emphasized and, in line with the emerging evidence, aims to distinguish between primary disease and secondary outcome prevention. In the primary prevention of heart failure, it appears prudent advising obese individuals to lose or achieve a healthy body weight, especially in those with risk factors such as hypertension or type 2 diabetes. However, there is no evidence from clinical trials to guide weight management in overweight or obese patients with established heart failure. Prospective clinical trials are strongly encouraged.

Music close to one's heart: heart rate variability with music, diagnostic with e-bra and smartphone

NASA Astrophysics Data System (ADS)

Hegde, Shantala; Kumar, Prashanth S.; Rai, Pratyush; Mathur, Gyanesh N.; Varadan, Vijay K.

2012-04-01

Music is a powerful elicitor of emotions. Emotions evoked by music, through autonomic correlates have been shown to cause significant modulation of parameters like heart rate and blood pressure. Consequently, Heart Rate Variability (HRV) analysis can be a powerful tool to explore evidence based therapeutic functions of music and conduct empirical studies on effect of musical emotion on heart function. However, there are limitations with current studies. HRV analysis has produced variable results to different emotions evoked via music, owing to variability in the methodology and the nature of music chosen. Therefore, a pragmatic understanding of HRV correlates of musical emotion in individuals listening to specifically chosen music whilst carrying out day to day routine activities is needed. In the present study, we aim to study HRV as a single case study, using an e-bra with nano-sensors to record heart rate in real time. The e-bra developed previously, has several salient features that make it conducive for this study- fully integrated garment, dry electrodes for easy use and unrestricted mobility. The study considers two experimental conditions:- First, HRV will be recorded when there is no music in the background and second, when music chosen by the researcher and by the subject is playing in the background.

Management of Arrhythmias in Heart Failure

PubMed Central

Masarone, Daniele; Limongelli, Giuseppe; Rubino, Marta; Valente, Fabio; Vastarella, Rossella; Ammendola, Ernesto; Gravino, Rita; Verrengia, Marina; Salerno, Gemma; Pacileo, Giuseppe

2017-01-01

Heart failure patients are predisposed to develop arrhythmias. Supraventricular arrhythmias can exacerbate the heart failure symptoms by decreasing the effective cardiac output and their control require pharmacological, electrical, or catheter-based intervention. In the setting of atrial flutter or atrial fibrillation, anticoagulation becomes paramount to prevent systemic or cerebral embolism. Patients with heart failure are also prone to develop ventricular arrhythmias that can present a challenge to the managing clinician. The management strategy depends on the type of arrhythmia, the underlying structural heart disease, the severity of heart failure, and the range from optimization of heart failure therapy to catheter ablation. Patients with heart failure, irrespective of ejection fraction are at high risk for developing sudden cardiac death, however risk stratification is a clinical challenge and requires a multiparametric evaluation for identification of patients who should undergo implantation of a cardioverter defibrillator. Finally, patients with heart failure can also develop symptomatic bradycardia, caused by sinus node dysfunction or atrio-ventricular block. The treatment of bradycardia in these patients with pacing is usually straightforward but needs some specific issue. PMID:29367535

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

PubMed Central

DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2016-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new technologies portend an era of accelerated discovery of the earliest period of development. PMID:26303396

An integrated optical coherence microscopy imaging and optical stimulation system for optogenetic pacing in Drosophila melanogaster (Conference Presentation)

NASA Astrophysics Data System (ADS)

Alex, Aneesh; Li, Airong; Men, Jing; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

2016-03-01

Electrical stimulation is the clinical standard for cardiac pacing. Although highly effective in controlling cardiac rhythm, the invasive nature, non-specificity to cardiac tissues and possible tissue damage limits its applications. Optogenetic pacing of the heart is a promising alternative, which is non-invasive and more specific, has high spatial and temporal precision, and avoids the shortcomings in electrical stimulation. Drosophila melanogaster, which is a powerful model organism with orthologs of nearly 75% of human disease genes, has not been studied for optogenetic pacing in the heart. Here, we developed a non-invasive integrated optical pacing and optical coherence microscopy (OCM) imaging system to control the heart rhythm of Drosophila at different developmental stages using light. The OCM system is capable of providing high imaging speed (130 frames/s) and ultrahigh imaging resolutions (1.5 μm and 3.9 μm for axial and transverse resolutions, respectively). A light-sensitive pacemaker was developed in Drosophila by specifically expressing the light-gated cation channel, channelrhodopsin-2 (ChR2) in transgenic Drosophila heart. We achieved non-invasive and specific optical control of the Drosophila heart rhythm throughout the fly's life cycle (larva, pupa, and adult) by stimulating the heart with 475 nm pulsed laser light. Heart response to stimulation pulses was monitored non-invasively with OCM. This integrated non-invasive optogenetic control and in vivo imaging technique provides a novel platform for performing research studies in developmental cardiology.

[Effectiveness of heart tumor therapy in the cardiology department during 7 year follow-up].

PubMed

Dabek, Józefa; Twardowski, Romuald; Jakubowski, Daniel; Michniak, Barbara; Swiderski, Robert; Gasior, Zbigniew

2009-11-01

Neoplasms of the heart are rare. Usually asymptomatic on the early stage are diagnosed incidentally. Among primary heart neoplasms the most often benign tumors are diagnosed--mostly myxomas, whereas the majority of malignant heart tumors are sarcomas. The aim of this paper was to present heart tumors diagnosed in the cardiology department, their symptoms, used diagnostic tests and therapy and to show after therapy quality of life changes. There were 18 patients included to the study, whom during hospitalization in the cardiology department heart tumors were diagnosed. There were 11 women and 7 men, aged from 33- to 76-years-old (mean 60,5 years). To all of the patients medical interview, physical examination, EKG, UCG and laboratory test were performed. Additionally in some cases computed tomography or magnetic resonance imaging of the chest and coronary angiograms were done. Based on the diagnostic tests results the patients were qualified to conservative or surgical treatment. Among 18 heart tumor patients in 12 cases primary benign tumors were diagnosed (66,6%), 1 patient had primary malignant tumor (5,5%), there were 3 cases of metastatic tumors (16,6%) and 2 patients with non-neoplasmic tumors--clots (11,1%). From 18 subjects with heart tumor 3 patients died because of advanced stage of neoplasmic disease and presence of metastatic tumors in the heart. Results of the study show, that heart tumors, regardless of development of diagnostic tests, are still diagnosed too late. The study group follow-up proved, that early diagnosis and proper heart tumor treatment prevented complications and improved the quality of life. It is worth to emphasize, that coronary angiogram in some cases allowed to diagnose coronary artery disease, to treat heart tumor and to perform coronary artery by-pass grafting simultaneously.

Dentigenous infectious foci – a risk factor of infective endocarditis

PubMed Central

Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

2012-01-01

Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

Renal Denervation to Modify Hypertension and the Heart Failure State.

PubMed

Zhong, Ming; Kim, Luke K; Swaminathan, Rajesh V; Feldman, Dmitriy N

2017-07-01

Sympathetic overactivation of renal afferent and efferent nerves have been implicated in the development and maintenance of several cardiovascular disease states, including resistant hypertension and heart failure with both reduced and preserved systolic function. With the development of minimally invasive catheter-based techniques, percutaneous renal denervation has become a safe and effective method of attenuating sympathetic overactivation. Percutaneous renal denervation, therefore, has the potential to modify and treat hypertension and congestive heart failure. Although future randomized controlled studies are needed to definitively prove its efficacy, renal denervation has the potential to change the way we view and treat cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental cardiovascular physiology of the olive ridley sea turtle (Lepidochelys olivacea).

PubMed

Crossley, Dane Alan; Crossley, Janna Lee; Smith, Camilla; Harfush, Martha; Sánchez-Sánchez, Hermilo; Garduño-Paz, Mónica Vanessa; Méndez-Sánchez, José Fernando

2017-09-01

Our understanding of reptilian cardiovascular development and regulation has increased substantially for two species the American alligator (Alligator mississippiensis) and the common snapping turtle (Chelydra serpentina) during the past two decades. However, what we know about cardiovascular maturation in many other species remains poorly understood or unknown. Embryonic sea turtles have been studied to understand the maturation of metabolic function, but these studies have not addressed the cardiovascular system. Although prior studies have been pivotal in characterizing development, and factors that influence it, the development of cardiovascular function, which supplies metabolic function, is unknown in sea turtles. During our investigation we focused on quantifying how cardiovascular morphological and functional parameters change, to provide basic knowledge of development in the olive ridley sea turtle (Lepidochelys olivacea). Embryonic mass, as well as mass of the heart, lungs, liver, kidney, and brain increased during turtle embryo development. Although heart rate was constant during this developmental period, arterial pressure approximately doubled. Further, while embryonic olive ridley sea turtles lacked cholinergic tone on heart rate, there was a pronounced beta adrenergic tone on heart rate that decreased in strength at 90% of incubation. This beta adrenergic tone may be partially originating from the sympathetic nervous system at 90% of incubation, with the majority originating from circulating catecholamines. Data indicates that olive ridley sea turtles share traits of embryonic functional cardiovascular maturation with the American alligator (Alligator mississippiensis) but not the common snapping turtle (Chelydra serpentina). Copyright © 2017 Elsevier Inc. All rights reserved.

A Human-Centered Approach to CV Care: Infrastructure Development in Uganda.

PubMed

Longenecker, Christopher T; Kalra, Ankur; Okello, Emmy; Lwabi, Peter; Omagino, John O; Kityo, Cissy; Kamya, Moses R; Webel, Allison R; Simon, Daniel I; Salata, Robert A; Costa, Marco A

2018-04-20

In this case study, we describe an ongoing approach to develop sustainable acute and chronic cardiovascular care infrastructure in Uganda that involves patient and provider participation. Leveraging strong infrastructure for HIV/AIDS care delivery, University Hospitals Harrington Heart and Vascular Institute and Case Western Reserve University have partnered with U.S. and Ugandan collaborators to improve cardiovascular capabilities. The collaboration has solicited innovative solutions from patients and providers focusing on education and advanced training, penicillin supply, diagnostic strategy (e.g., hand-held ultrasound), maternal health, and community awareness. Key outcomes of this approach have been the completion of formal training of the first interventional cardiologists and heart failure specialists in the country, establishment of 4 integrated regional centers of excellence in rheumatic heart disease care with a national rheumatic heart disease registry, a penicillin distribution and adherence support program focused on retention in care, access to imaging technology, and in-country capabilities to treat advanced rheumatic heart valve disease. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Divergent Requirements for EZH1 in Heart Development Versus Regeneration.

PubMed

Ai, Shanshan; Yu, Xianhong; Li, Yumei; Peng, Yong; Li, Chen; Yue, Yanzhu; Tao, Ge; Li, Chuanyun; Pu, William T; He, Aibin

2017-07-07

Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Heart development was normal in Ezh1 -/- ( Ezh 1 knockout) and Ezh2 f/f ::cTNT -Cre ( Ezh 2 knockout) embryos. Ablation of both genes in Ezh1 -/- ::Ezh2 f/f ::cTNT -Cre embryos caused lethal heart malformations, including hypertrabeculation, compact myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome profiling showed that derepressed genes were upregulated in a manner consistent with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2 was dispensable. This finding was further supported by rescue experiments: cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal heart regeneration in Ezh 1 knockout. In myocardial infarction performed outside of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1 occupied and activated genes related to cardiac growth. Our work unravels divergent mechanisms of EZH1 in heart development and regeneration, which will empower efforts to overcome epigenetic barriers to heart regeneration. © 2017 American Heart Association, Inc.

[Cohort study of ischemic heart disease among 1817 workers in a foundry].

PubMed

Lu, Yang; Zhang, Min

2012-09-01

To determine the risk of ischemic heart disease among foundry workers and the exposure-response relationship between the risk and foundry work and cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing ischemic heart disease by a given length of employment and exposure to silica dust in foundry workers. Cohort study was conducted, following-up workers in an automobile foundry employed for more than one year during January 1, 1980 to December 31, 1996 as cohort members. In total, 30 years were followed to December 31, 2009. In cohort, workers exposed to pouring, sand preparation, cast shakeout and finishing, melting, overhead crane operation, moulding and core-making were in foundry group, and auxiliary workers at the same factory, such as electricians, fitters, and inspectors were in control group. The risk of ischemic heart disease among foundry workers and the exposure-response relationship between the risk and foundry work and cumulative exposure to silica dust were analyzed with cox regression model using SPSS software, and a logistic regression model was established for prediction of risk for developing ischemic heart disease at a given length of employment and exposure to silica dust in foundry workers. Totally, 1817 workers were followed-up for 45 553.05 person-years during 30 years, with 156 cases of ischemic heart disease and incidence of 342.46 per 100 000 person-years. And the average age at onset was 51.46 years and duration of employment at onset was 21.61 years. Results showed that male, smoking, alcohol drinking, age and duration of employment were risk factors for ischemic heart disease. Risk of ischemic heart disease in foundry workers positively correlated with cumulative silica exposure, and the risk of ischemic heart disease increased by 75.8 percent (RR = 1.758, 95% CI 1.221-2.532) with cumulative silica exposure of 1 mg/m3 x year, adjusted for smoking. And risk of ischemic heart disease was significantly higher in the exposed group than that in the control one. Compared with control group workers, risk of ischemic heart disease increased by 1.048 folds, 1.395 folds, 70.4 percent, 97.0 percent and 1.270 folds among workers exposed to sand preparation, cast shakeout and finishing, melting, moulding and core-making, respectively, adjusted for smoking. Based on the predictive of model, risk for developing ischemic heart disease increased with the length of employment and exposure to silica dust in foundry workers. Workers in foundry face high risk of ischemic heart disease. Risk of ischemic heart disease varies by job, which is higher in workers exposed to sand preparation, cast shakeout and finishing, melting, moulding and core-making. Both foundry work and cumulative exposure to silica are risk factors. The model for prediction of risk for developing ischemic heart disease at a given length of employment and exposure to silica dust in foundry workers resulted in a valid exposure-response relationship.

Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects.

PubMed

Mäenpää, Heidi; Häkkinen, Arja; Sarajuuri, Anne

2016-01-01

To compare changes in motor development from 1 to 5 years of age among 18 children with hypoplastic left heart syndrome and 12 with univentricular heart to 42 children without heart defect. Motor development was assessed with the Alberta Infant Motor Scale and Movement Assessment Battery for Children (Movement ABC). Children with hypoplastic left heart syndrome or univentricular heart had significantly lower scores on the Alberta Infant Motor Scale test at the age of 1 and on the Movement ABC test at the age of 5 years compared with controls. Children with clear abnormalities on brain magnetic resonance imaging had lower scores compared with those with normal images or mild changes, and their relative motor scores decreased during follow-up. Some children with univentricular heart defects may benefit from physiotherapeutic interventions to support their motor development.

In vivo wall shear measurements within the developing zebrafish heart.

PubMed

Jamison, R Aidan; Samarage, Chaminda R; Bryson-Richardson, Robert J; Fouras, Andreas

2013-01-01

Physical forces can influence the embryonic development of many tissues. Within the cardiovascular system shear forces resulting from blood flow are known to be one of the regulatory signals that shape the developing heart. A key challenge in investigating the role of shear forces in cardiac development is the ability to obtain shear force measurements in vivo. Utilising the zebrafish model system we have developed a methodology that allows the shear force within the developing embryonic heart to be determined. Accurate wall shear measurement requires two essential pieces of information; high-resolution velocity measurements near the heart wall and the location and orientation of the heart wall itself. We have applied high-speed brightfield imaging to capture time-lapse series of blood flow within the beating heart between 3 and 6 days post-fertilization. Cardiac-phase filtering is applied to these time-lapse images to remove the heart wall and other slow moving structures leaving only the red blood cell movement. Using particle image velocimetry to calculate the velocity of red blood cells in different regions within the heart, and using the signal-to-noise ratio of the cardiac-phase filtered images to determine the boundary of blood flow, and therefore the position of the heart wall, we have been able to generate the necessary information to measure wall shear in vivo. We describe the methodology required to measure shear in vivo and the application of this technique to the developing zebrafish heart. We identify a reduction in shear at the ventricular-bulbar valve between 3 and 6 days post-fertilization and demonstrate that the shear environment of the ventricle during systole is constantly developing towards a more uniform level.

Usefulness of Tricuspid Annular Diameter to Predict Late Right Sided Heart Failure in Patients With Left Ventricular Assist Device.

PubMed

Nakanishi, Koki; Homma, Shunichi; Han, Jiho; Takayama, Hiroo; Colombo, Paolo C; Yuzefpolskaya, Melana; Garan, Arthur R; Farr, Maryjane A; Kurlansky, Paul; Di Tullio, Marco R; Naka, Yoshifumi; Takeda, Koji

2018-07-01

Although late-onset right-sided heart failure is recognized as a clinical problem in the treatment of patients with left ventricular assist devices (LVADs), the mechanism and predictors are unknown. Tricuspid valve (TV) deformation leads to the restriction of the leaflet motion and decreased coaptation, resulting in a functional tricuspid regurgitation that may act as a surrogate marker of late right-sided heart failure. This study aimed to investigate the association of preoperative TV deformation (annulus dilatation and leaflet tethering) with late right-sided heart failure development after continuous-flow LVAD implantation. The study cohort consisted of 274 patients who underwent 2-dimensional echocardiography before LVAD implantation. TV annulus diameter and tethering distance were measured in an apical 4-chamber view. Late right-sided heart failure was defined as right-sided heart failure requiring readmission and medical and/or surgical treatment after initial LVAD implantation. During a mean follow-up of 25.1 ± 19.0 months after LVAD implantation, late right-sided heart failure occurred in 33 patients (12.0%). Multivariate Cox proportional hazard analysis demonstrated that TV annulus diameter (hazard ratio 1.221 per 1 mm, p <0.001) was significantly associated with late right-sided heart failure development, whereas leaflet tethering distance was not. The best cut-off value of the TV annular diameter was 41 mm (area under the curve 0.787). Kaplan-Meier analysis showed that patients with dilated TV annulus (TV annular diameter ≥41 mm) exhibited a significantly higher late right-sided heart failure occurrence than those without TV annular enlargement (log-rank p <0.001). In conclusion, preoperative TV annulus diameter, but not leaflet tethering distance, predicted the occurrence of late right-sided heart failure after LVAD implantation. Copyright © 2018 Elsevier Inc. All rights reserved.

Paraoxonase 2 prevents the development of heart failure.

PubMed

Li, Wei; Kennedy, David; Shao, Zhili; Wang, Xi; Kamdar, Andre Klaassen; Weber, Malory; Mislick, Kayla; Kiefer, Kathryn; Morales, Rommel; Agatisa-Boyle, Brendan; Shih, Diana M; Reddy, Srinivasa T; Moravec, Christine S; Tang, W H Wilson

2018-05-02

Mitochondrial oxidation is a major source of reactive oxygen species (ROS) and mitochondrial dysfunction plays a central role in development of heart failure (HF). Paraoxonase 2 deficient (PON2-def) mitochondria are impaired in function. In this study, we tested whether PON2-def aggravates HF progression. Using qPCR, immunoblotting and lactonase activity assay, we demonstrate that PON2 activity was significantly decreased in failing hearts despite increased PON2 expression. To determine the cardiac-specific function of PON2, we performed heart transplantations in which PON2-def and wild type (WT) donor hearts were implanted into WT recipient mice. Beating scores of the donor hearts, assessed at 4 weeks post-transplantation, were significantly decreased in PON2-def hearts when compared to WT donor hearts. By using a transverse aortic constriction (TAC) model, we found PON2 deficiency significantly exacerbated left ventricular remodeling and cardiac fibrosis post-TAC. We further demonstrated PON2 deficiency significantly enhanced ROS generation in heart tissues post-TAC. ROS generation was measured through dihydroethidium (DHE) using high-pressure liquid chromatography (HPLC) with a fluorescent detector. By using neonatal cardiomyocytes treated with CoCl 2 to mimic hypoxia, we found PON2 deficiency dramatically increased ROS generation in the cardiomyocytes upon CoCl 2 treatment. In response to a short CoCl 2 exposure, cell viability and succinate dehydrogenase (SDH) activity assessed by MTT assay were significantly diminished in PON2-def cardiomyocytes compared to those in WT cardiomyocytes. PON2-def cardiomyocytes also had lower baseline SDH activity. By using adult mouse cardiomyocytes and mitochondrial ToxGlo assay, we found impaired cellular ATP generation in PON2-def cells compared to that in WT cells, suggesting that PON2 is necessary for proper mitochondrial function. Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement and classification of heart and lung sounds by using LabView for educational use.

PubMed

Altrabsheh, B

2010-01-01

This study presents the design, development and implementation of a simple low-cost method of phonocardiography signal detection. Human heart and lung signals are detected by using a simple microphone through a personal computer; the signals are recorded and analysed using LabView software. Amplitude and frequency analyses are carried out for various phonocardiography pathological cases. Methods for automatic classification of normal and abnormal heart sounds, murmurs and lung sounds are presented. Various cases of heart and lung sound measurement are recorded and analysed. The measurements can be saved for further analysis. The method in this study can be used by doctors as a detection tool aid and may be useful for teaching purposes at medical and nursing schools.

Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort.

PubMed

Dubin, Ruth F; Deo, Rajat; Bansal, Nisha; Anderson, Amanda H; Yang, Peter; Go, Alan S; Keane, Martin; Townsend, Ray; Porter, Anna; Budoff, Matthew; Malik, Shaista; He, Jiang; Rahman, Mahboob; Wright, Jackson; Cappola, Thomas; Kallem, Radhakrishna; Roy, Jason; Sha, Daohang; Shlipak, Michael G

2017-01-06

Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD. We evaluated echocardiograms of 2567 participants without self-reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height 2.7 , and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7-7.6) years. Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m 2 . During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B-type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death. Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers. Copyright © 2016 by the American Society of Nephrology.

Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort

PubMed Central

Deo, Rajat; Bansal, Nisha; Anderson, Amanda H.; Yang, Peter; Go, Alan S.; Keane, Martin; Townsend, Ray; Porter, Anna; Budoff, Matthew; Malik, Shaista; He, Jiang; Rahman, Mahboob; Wright, Jackson; Cappola, Thomas; Kallem, Radhakrishna; Roy, Jason; Sha, Daohang; Shlipak, Michael G.

2017-01-01

Background and objectives Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD. Design, setting, participants, & measurements We evaluated echocardiograms of 2567 participants without self–reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height2.7, and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7–7.6) years. Results Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59±11 years old, and mean eGFR was 44±17 ml/min per 1.73 m2. During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B–type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death. Conclusions Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers. PMID:28062676

Cognitive impairment and cardiovascular diseases in the elderly. A heart-brain continuum hypothesis.

PubMed

Abete, Pasquale; Della-Morte, David; Gargiulo, Gaetano; Basile, Claudia; Langellotto, Assunta; Galizia, Gianluigi; Testa, Gianluca; Canonico, Vincenzo; Bonaduce, Domenico; Cacciatore, Francesco

2014-11-01

The aging population is increasing and, therefore, a higher prevalence of cardiac disease is emerging; including hypertension, coronary artery disease, atrial fibrillation and chronic heart failure. Large cohort studies have revealed a relationship among increased risk for cognitive impairment and dementia in cardiovascular diseases probably due to embolic stroke or chronic cerebral hypoperfusion. Thus, the aim of the present review is to overview the studies that investigate the presence and/or the development of cognitive impairments and dementia in patients with varied types of cardiovascular disease. Finally, a continuum among hypertension, coronary artery disease, atrial fibrillation and chronic heart failure with to the development of cognitive impairment and progression to dementia has been hypothesized. Copyright © 2014 Elsevier B.V. All rights reserved.

Carvedilol case history: the discovery and development of the first β-blocker for the treatment of congestive heart failure.

PubMed

Ruffolo, Robert R; Feuerstein, Giora Z

2006-06-01

Carvedilol is a multiple action drug that blocks β1-, β2- and α1- adrenoceptors, and has potent antioxidant properties. Carvedilol is the first drug of its kind to be approved for the treatment of congestive heart failure, and is now the standard of care for this devastating disease. The discovery and development of carvedilol encountered an adverse regulatory climate, skepticism by the cardiology community and hesitance by the company, and in the early 1990s, the fate of the drug was uncertain. Nonetheless, in the largest heart failure study conducted up until that point, carvedilol produced marked reductions in morbidity and mortality, and has given new hope to patients afflicted with congestive heart failure. The story behind carvedilol contains important observations and lessons for scientists, regulators and physicians.

Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

PubMed

Zhang, Hongmei; Dong, Yan; Su, Qing

2017-02-01

In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

Reappearance of beriberi heart disease in Japan. A study of 23 cases.

PubMed

Kawai, C; Wakabayashi, A; Matsumura, T; Yui, Y

1980-09-01

Twenty-three Japanese patients with beriberi heart disease, 17 of them teenagers, were studied. The recent tendency for teenagers to take excessive sweet carbonated soft drinks, instant noodles and powermill-polished rice readily induces relative thiamine deficiency. A sudden increase in thiamine requirements due to strenuous exercise can result in overt beriberi heart disease. Alcohol had nothing to do with the development of the disease. Characteristic features commonly seen in teenage patients include peripheral edema, low peripheral vascular resistance, increased venous pressure enlarged heart, T wave abnormalities, hyperkinetic circulatory state and increased circulating blood volume. Thiamine deficiency was confirmed by a decrease in blood thiamine concentration, a decrease in erythrocyte transketolase activity and an increase in thiamine pyrophosphate (TPP) effect. Improvement was rapidly achieved with thiamine administration, balanced nutrition and rest, especially in the teenage patients. Increased circulating blood volume was useful in differentiating beriberi heart disease from hyperthyroidism.

Vasodilators in Acute Heart Failure: Review of the Latest Studies.

PubMed

Levy, Phillip D; Laribi, Said; Mebazaa, Alexandre

2014-06-01

Vasodilators play an important role in the management of acute heart failure, particularly when increased afterload is the precipitating cause of decompensation. The time-honored approach to afterload reduction has been largely focused on use of intravenous nitrovasodilators and, when properly dosed, this class of agents does provide substantial symptom relief for patients with acute hypertensive heart failure. Despite this, nitrovasodilators have never been shown to diminish mortality or provide any post-discharge outcome benefit leading to an on-going search for viable and more effective alternatives. While no new vasodilators have been approved for use in acute heart failure since nesiritide more than a decade ago, a number of novel agents have been developed, with some showing significant promise in recent clinical trials. In this review, we summarize the latest study data as it relates to vasodilator therapy and provide a glimpse into the not too distant future state of acute heart failure care.

Identification and Progression of Heart Disease Risk Factors in Diabetic Patients from Longitudinal Electronic Health Records.

PubMed

Jonnagaddala, Jitendra; Liaw, Siaw-Teng; Ray, Pradeep; Kumar, Manish; Dai, Hong-Jie; Hsu, Chien-Yeh

2015-01-01

Heart disease is the leading cause of death worldwide. Therefore, assessing the risk of its occurrence is a crucial step in predicting serious cardiac events. Identifying heart disease risk factors and tracking their progression is a preliminary step in heart disease risk assessment. A large number of studies have reported the use of risk factor data collected prospectively. Electronic health record systems are a great resource of the required risk factor data. Unfortunately, most of the valuable information on risk factor data is buried in the form of unstructured clinical notes in electronic health records. In this study, we present an information extraction system to extract related information on heart disease risk factors from unstructured clinical notes using a hybrid approach. The hybrid approach employs both machine learning and rule-based clinical text mining techniques. The developed system achieved an overall microaveraged F-score of 0.8302.

Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.

PubMed

Wiklund, Ingela; Anatchkova, Milena; Oko-Osi, Hafiz; von Maltzahn, Robyn; Chau, Dina; Malik, Fady I; Patrick, Donald L; Spertus, John; Teerlink, John R

2016-09-15

Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process. Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items. During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders. Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.

Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries

PubMed Central

Narematsu, Mayu; Kamimura, Tatsuya; Yamagishi, Toshiyuki; Fukui, Mitsuru; Nakajima, Yuji

2015-01-01

Background Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart progenitors that originated from the left and right AHF migrate to form distinct conotruncal regions. The aim of this study is to identify abnormal AHF development that causes the morphology of transposition of the great arteries. Methods and Results We placed a retinoic acid–soaked bead on the left or the right or on both sides of the AHF of stage 12 to 14 chick embryos and examined the conotruncal heart defect at stage 34. Transposition of the great arteries was diagnosed at high incidence in embryos for which a retinoic acid–soaked bead had been placed in the left AHF at stage 12. Fluorescent dye tracing showed that AHF exposed to retinoic acid failed to contribute to conotruncus development. FGF8 and Isl1 expression were downregulated in retinoic acid–exposed AHF, and differentiation and expansion of cardiomyocytes were suppressed in cultured AHF in medium supplemented with retinoic acid. Conclusions The left AHF at the early looped heart stage, corresponding to Carnegie stages 10 to 11 (28 to 29 days after fertilization) in human embryos, is the region of the impediment that causes the morphology of transposition of the great arteries. PMID:25929268

Measurement of functional capacity requirements to aid in development of an occupation-specific rehabilitation training program to help firefighters with cardiac disease safely return to work.

PubMed

Adams, Jenny; Roberts, Joanne; Simms, Kay; Cheng, Dunlei; Hartman, Julie; Bartlett, Charles

2009-03-15

We designed a study to measure the functional capacity requirements of firefighters to aid in the development of an occupation-specific training program in cardiac rehabilitation; 23 healthy male firefighters with no history of heart disease completed a fire and rescue obstacle course that simulated 7 common firefighting tasks. They wore complete personal protective equipment and portable metabolic instruments that included a data collection mask. We monitored each subject's oxygen consumption (VO(2)) and working heart rate, then calculated age-predicted maximum heart rates (220 - age) and training target heart rates (85% of age-predicted maximum heart rate). During performance of the obstacle course, the subjects' mean working heart rates and peak heart rates were higher than the calculated training target heart rates (t(22) = 5.69 [working vs target, p <0.001] and t(22) = 15.14 [peak vs target, p <0.001]). These findings, with mean results for peak VO(2) (3,447 ml/min) and metabolic equivalents (11.9 METs), show that our subjects' functional capacity greatly exceeded that typically attained by patients in traditional cardiac rehabilitation programs (5 to 8 METs). In conclusion, our results indicate the need for intense, occupation-specific cardiac rehabilitation training that will help firefighters safely return to work after a cardiac event.

Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure.

PubMed

Chowdhury, Biswajit; Xiang, Bo; Liu, Michelle; Hemming, Richard; Dolinsky, Vernon W; Triggs-Raine, Barbara

2017-01-01

Hyaluronan (HA) is required for endothelial-to-mesenchymal transition and normal heart development in the mouse. Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient ( Hyal2 - /- ) mice and humans suggested removal of HA is also important for normal heart development. We have performed longitudinal studies of heart structure and function in Hyal2 -/- mice to determine when, and how, HYAL2 deficiency leads to these abnormalities. Echocardiography revealed atrial enlargement, atrial tissue masses, and valvular thickening at 4 weeks of age, as well as diastolic dysfunction that progressed with age, in Hyal2 -/- mice. These abnormalities were associated with increased HA, vimentin-positive cells, and fibrosis in Hyal2 -/- compared with control mice. Based on the severity of heart dysfunction, acute and chronic groups of Hyal2 -/- mice that died at an average of 12 and 25 weeks respectively, were defined. Increased HA levels and mesenchymal cells, but not vascular endothelial growth factor in Hyal2 -/- embryonic hearts, suggest that HYAL2 is important to inhibit endothelial-to-mesenchymal transition. Consistent with this, in wild-type embryos, HYAL2 and HA were readily detected, and HA levels decreased with age. These data demonstrate that disruption of normal HA catabolism in Hyal2 -/- mice causes increased HA, which may promote endothelial-to-mesenchymal transition and proliferation of mesenchymal cells. Excess endothelial-to-mesenchymal transition, resulting in increased mesenchymal cells, is the likely cause of morphological heart abnormalities in both humans and mice. In mice, these abnormalities result in progressive and severe diastolic dysfunction, culminating in heart failure. © 2016 The Authors.

Endocarditis in left ventricular assist device

PubMed Central

Thyagarajan, Braghadheeswar; Kumar, Monisha Priyadarshini; Sikachi, Rutuja R; Agrawal, Abhinav

2016-01-01

Summary Heart failure is one of the leading causes of death in developed nations. End stage heart failure often requires cardiac transplantation for survival. The left ventricular assist device (LVAD) has been one of the biggest evolvements in heart failure management often serving as bridge to transplant or destination therapy in advanced heart failure. Like any other medical device, LVAD is associated with complications with infections being reported in many patients. Endocarditis developing secondary to the placement of LVAD is not a frequent, serious and difficult to treat condition with high morbidity and mortality. Currently, there are few retrospective studies and case reports reporting the same. In our review, we found the most common cause of endocarditis in LVAD was due to bacteria. Both bacterial and fungal endocarditis were associated with high morbidity and mortality. In this review we will be discussing the risk factors, organisms involved, diagnostic tests, management strategies, complications, and outcomes in patients who developed endocarditis secondary to LVAD placement. PMID:27672540

Quality of Life for Saudi Patients With Heart Failure: A Cross-Sectional Correlational Study.

PubMed

AbuRuz, Mohannad Eid; Alaloul, Fawwaz; Saifan, Ahmed; Masa'deh, Rami; Abusalem, Said

2015-06-25

Heart failure is a major public health issue and a growing concern in developing countries, including Saudi Arabia. Most related research was conducted in Western cultures and may have limited applicability for individuals in Saudi Arabia. Thus, this study assesses the quality of life of Saudi patients with heart failure. A cross-sectional correlational design was used on a convenient sample of 103 patients with heart failure. Data were collected using the Short Form-36 and the Medical Outcomes Study-Social Support Survey. Overall, the patients' scores were low for all domains of Quality of Life. The Physical Component Summary and Mental Component Summary mean scores and SDs were (36.7±12.4, 48.8±6.5) respectively, indicating poor Quality of Life. Left ventricular ejection fraction was the strongest predictor of both physical and mental summaries. Identifying factors that impact quality of life for Saudi heart failure patients is important in identifying and meeting their physical and psychosocial needs.

Potential of resveratrol in the treatment of heart failure.

PubMed

Raj, Pema; Louis, Xavier Lieben; Thandapilly, Sijo Joseph; Movahed, Ali; Zieroth, Shelley; Netticadan, Thomas

2014-01-30

The concept of food has expanded beyond its traditional role of survival and hunger satisfaction, to include a role in the prevention and treatment of disease. Polyphenols are classes of compounds that are synthesized by plants to serve a wide variety of functions including growth pollination and defense. These compounds have recently received increased attention in medical research. In this group, one of the most studied has been resveratrol (3,5,4,-trihydroxystilbene), a polyphenol, which is found predominantly in grapes and berries. Over the past two decades, researchers have studied the ability of resveratrol to prevent or reverse the development of abnormalities in heart structure and function in animal models of heart disease and heart failure. The results from animal studies have been promising, and very recently, this knowledge has been translated into examining the efficacy of resveratrol in humans with heart disease/failure. In this review we will discuss the current status of resveratrol research on cardioprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased Regurgitant Flow Causes Endocardial Cushion Defects in an Avian Embryonic Model of Congenital Heart Disease

PubMed Central

Ford, Stephanie M; McPheeters, Matthew T; Wang, Yves T; Ma, Pei; Gu, Shi; Strainic, James; Snyder, Christopher; Rollins, Andrew M; Watanabe, Michiko; Jenkins, Michael W

2017-01-01

Background The relationship between changes in endocardial cushion and resultant congenital heart diseases (CHD) has yet to be established. It has been shown that increased regurgitant flow early in embryonic heart development leads to endocardial cushion defects, but it remains unclear how abnormal endocardial cushions during the looping stages might affect the fully septated heart. The goal of this study was to reproducibly alter blood flow in vivo and then quantify the resultant effects on morphology of endocardial cushions in the looping heart and on CHDs in the septated heart. Methods Optical pacing was applied to create regurgitant flow in embryonic hearts, and optical coherence tomography (OCT) was utilized to quantify regurgitation and morphology. Embryonic quail hearts were optically paced at 3 Hz (180bpm, well above intrinsic rate 60–110bpm) at stage 13 of development (3–4 wks human) for 5 min. Pacing fatigued the heart and led to at least 1 hr of increased regurgitant flow. Resultant morphological changes were quantified with OCT imaging at stage 19 (cardiac looping – 4–5 wks human) or stage 35 (4 chambered heart – 8 wks human). Results All paced embryos imaged at stage 19 displayed structural changes in cardiac cushions. The amount of regurgitant flow immediately after pacing was inversely correlated with cardiac cushion size 24-hrs post pacing (p-value < 0.01). The embryos with the most regurgitant flow and smallest cushions after pacing had a decreased survival rate at 8 days (p<0.05), indicating that those most severe endocardial cushion defects were lethal. Of the embryos that survived to stage 35, 17/18 exhibited CHDs including valve defects, ventricular septal defects, hypoplastic ventricles, and common AV canal. Conclusion The data illustrate a strong inverse relationship in which regurgitant flow precedes abnormal and smaller cardiac cushions, resulting in the development of CHDs. PMID:28211263

Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

PubMed

Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

2017-06-14

Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The Obesity and Heart Failure Epidemics Among African Americans: Insights From the Jackson Heart Study.

PubMed

Krishnamoorthy, Arun; Greiner, Melissa A; Bertoni, Alain G; Eapen, Zubin J; O'Brien, Emily C; Curtis, Lesley H; Hernandez, Adrian F; Mentz, Robert J

2016-08-01

Higher rates of obesity and heart failure have been observed in African Americans, but associations with mortality are not well-described. We examined intermediate and long-term clinical implications of obesity in African Americans and associations between obesity and all-cause mortality, heart failure, and heart failure hospitalization. We conducted a retrospective analysis of a community sample of 5292 African Americans participating in the Jackson Heart Study between September 2000 and January 2013. The main outcomes were associations between body mass index (BMI) and all-cause mortality at 9 years and heart failure hospitalization at 7 years using Cox proportional hazards models and interval development of heart failure (median 8 years' follow-up) using a modified Poisson model. At baseline, 1406 (27%) participants were obese and 1416 (27%) were morbidly obese. With increasing BMI, the cumulative incidence of mortality decreased (P= .007), whereas heart failure increased (P < .001). Heart failure hospitalization was more common among morbidly obese participants (9.0%; 95% confidence interval [CI] 7.6-11.7) than among normal-weight patients (6.3%; 95% CI 4.7-8.4). After risk adjustment, BMI was not associated with mortality. Each 1-point increase in BMI was associated with a 5% increase in the risk of heart failure (hazard ratio 1.05; 95% CI 1.03-1.06; P < .001) and the risk of heart failure hospitalization for BMI greater than 32 kg/m(2) (hazard ratio 1.05; 95% CI 1.03-1.07; P < .001). Obesity and morbid obesity were common in a community sample of African Americans, and both were associated with increased heart failure and heart failure hospitalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Heart Check: The Development and Evolution of an Organizational Heart Health Assessment.

ERIC Educational Resources Information Center

Golaszewski, Thomas; Fisher, Brian

2002-01-01

Documented the development, testing, and application of an organizational assessment tool for measuring employer support for heart health. The Heart Check inventory measured such factors as organizational foundations, administrative supports, stress management, and screening services. Data on diverse worksites throughout New York State indicated…

Physiological response of cardiac tissue to bisphenol a: alterations in ventricular pressure and contractility

PubMed Central

Brooks, Daina; Chandra, Akhil; Jaimes, Rafael; Sarvazyan, Narine; Kay, Matthew

2015-01-01

Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts. In the present study, we tested if BPA exposure also adversely affects cardiac contractile performance. We examined the impact of BPA exposure level, sex, and pacing rate on cardiac contractile function in excised rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to 10−9-10−4 M BPA. Left ventricular developed pressure and contractility were measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca2+ transients were imaged from whole hearts and from neonatal rat cardiomyocyte layers. During sinus rhythm in female hearts, BPA exposure decreased left ventricular developed pressure and inotropy in a dose-dependent manner. The reduced contractile performance was exacerbated at higher pacing rates. BPA-induced effects on contractile performance were also observed in male hearts, albeit to a lesser extent. Exposure to BPA altered Ca2+ handling within whole hearts (reduced diastolic and systolic Ca2+ transient potentiation) and neonatal cardiomyocytes (reduced Ca2+ transient amplitude and prolonged Ca2+ transient release time). In conclusion, BPA exposure significantly impaired cardiac performance in a dose-dependent manner, having a major negative impact upon electrical conduction, intracellular Ca2+ handing, and ventricular contractility. PMID:25980024

The Anti-Coronary Club: 1957 to 1972.

PubMed

Singman, H S; Berman, S N; Cowell, C; Maslansky, E; Archer, M

1980-06-01

The Diet and Coronary Heart Disease Study Project, known as the Anti-Coronary Club, was established by the New York City Department of Health, Bureau of Nutrition in June 1957. The major goals were: 1) to develop an acceptable experimental diet capable of reducing serum cholesterol in ambulatory middle-aged men; and 2) to test the hypothesis that a reduction in serum cholesterol is associated with a modified diet and a reduced incidence of coronary heart disease development. The Prudent Diet was developed to provide a way of eating consistent with the American dietary pattern, avoiding an excess of empty calories, saturated fat, and food cholesterol. It provides a favorable balance of nutrients, limits total fat content and makes possible a more desirable ratio of PUFA to saturated fats. Based on the data, it seems reasonable to attribute the lower coronary heart disease incidence rates in the active experimental group of both age categories studied (40 to 49 and 50 to 59) directly to the reduction in serum cholesterol levels, with weight reduction as a beneficial accomplishment. Dietary intervention with the Prudent Diet was instrumental in achieving the lower coronary heart disease incidence rates that demonstrated the efficacy of the Prudent Diet as a sensible diet.

Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

PubMed

Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

2015-07-01

The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

Right heart failure: toward a common language.

PubMed

Mehra, Mandeep R; Park, Myung H; Landzberg, Michael J; Lala, Anuradha; Waxman, Aaron B

2014-02-01

In this perspective, the International Right Heart Foundation Working Group moves a step forward to develop a common language to describe the development and defects that exemplify the common syndrome of right heart failure. We first propose fundamental definitions of the distinctive components of the right heart circulation and provide consensus on a universal definition of right heart failure. These definitions will form the foundation for describing a uniform nomenclature for right heart circulatory failure with a view to foster collaborative research initiatives and conjoint education in an effort to provide insight into echanisms of disease unique to the right heart. © 2014 Published by International Society for the Heart and Lung Transplantation on behalf of International Society for Heart and Lung Transplantation.

Risks and costs of end-stage renal disease after heart transplantation.

PubMed

Hornberger, J; Best, J; Geppert, J; McClellan, M

1998-12-27

To estimate the risks and costs of end-stage renal disease (ESRD) after heart transplantation. Previous studies have shown high rates of ESRD among solid-organ transplant patients, but the relevance of these studies for current transplant practices and policies is unclear. Limitations of prior studies include relatively small, single-center samples and estimates made before implementing suggested practice changes to reduce ESRD risk. Medicare beneficiaries who underwent heart transplantation between 1989 and 1994 were eligible for study inclusion (n=2088). Thirty-four patients undergoing dialysis or who had the diagnosis of ESRD before or at transplantation were excluded from the study. ESRD was defined as any patient undergoing renal transplantation or requiring dialysis for more than 3 months. Mortality and ESRD events were recorded up to 1995. ESRD risk was estimated using the Kaplan-Meier product-limit estimator and logistic regression analyses. Linear regression was performed to determine expenditures for treating ESRD, and we developed long-term models of the risk and direct medical costs of ESRD care. The annual risk of ESRD was 0.37% in the first year after transplant and increased to 4.49% by the sixth posttransplant year. There was no significant trend in the risk of ESRD based on the year of transplantation, even after adjusting for patient characteristics. The average cumulative 10-year direct cost of ESRD per patient undergoing heart transplantation exceeded $13,000. In a large, national sample of patients undergoing heart transplantation, ESRD is not rare, even for patients undergoing transplant after the development of new practices intended to reduce its occurrence. ESRD remains an important component of the costs of heart transplantation.

Predictors of incident heart failure in patients after an acute coronary syndrome: The LIPID heart failure risk-prediction model.

PubMed

Driscoll, Andrea; Barnes, Elizabeth H; Blankenberg, Stefan; Colquhoun, David M; Hunt, David; Nestel, Paul J; Stewart, Ralph A; West, Malcolm J; White, Harvey D; Simes, John; Tonkin, Andrew

2017-12-01

Coronary heart disease is a major cause of heart failure. Availability of risk-prediction models that include both clinical parameters and biomarkers is limited. We aimed to develop such a model for prediction of incident heart failure. A multivariable risk-factor model was developed for prediction of first occurrence of heart failure death or hospitalization. A simplified risk score was derived that enabled subjects to be grouped into categories of 5-year risk varying from <5% to >20%. Among 7101 patients from the LIPID study (84% male), with median age 61years (interquartile range 55-67years), 558 (8%) died or were hospitalized because of heart failure. Older age, history of claudication or diabetes mellitus, body mass index>30kg/m 2 , LDL-cholesterol >2.5mmol/L, heart rate>70 beats/min, white blood cell count, and the nature of the qualifying acute coronary syndrome (myocardial infarction or unstable angina) were associated with an increase in heart failure events. Coronary revascularization was associated with a lower event rate. Incident heart failure increased with higher concentrations of B-type natriuretic peptide >50ng/L, cystatin C>0.93nmol/L, D-dimer >273nmol/L, high-sensitivity C-reactive protein >4.8nmol/L, and sensitive troponin I>0.018μg/L. Addition of biomarkers to the clinical risk model improved the model's C statistic from 0.73 to 0.77. The net reclassification improvement incorporating biomarkers into the clinical model using categories of 5-year risk was 23%. Adding a multibiomarker panel to conventional parameters markedly improved discrimination and risk classification for future heart failure events. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Design Thinking for mHealth Application Co-Design to Support Heart Failure Self-Management.

PubMed

Woods, Leanna; Cummings, Elizabeth; Duff, Jed; Walker, Kim

2017-01-01

Heart failure is a prevalent, progressive chronic disease costing in excess of $1billion per year in Australia alone. Disease self-management has positive implications for the patient and decreases healthcare usage. However, adherence to recommended guidelines is challenging and existing literature reports sub-optimal adherence. mHealth applications in chronic disease education have the potential to facilitate patient enablement for disease self-management. To the best of our knowledge no heart failure self-management application is available for safe use by our patients. In this paper, we present the process established to co-design a mHealth application in support of heart-failure self-management. For this development, an interdisciplinary team systematically proceeds through the phases of Stanford University's Design Thinking process; empathise, define, ideate, prototype and test with a user-centred philosophy. Using this clinician-led heart failure app research as a case study, we describe a sequence of procedures to engage with local patients, carers, software developers, eHealth experts and clinical colleagues to foster rigorously developed and locally relevant patient-facing mHealth solutions. Importantly, patients are engaged in each stage with ethnographic interviews, a series of workshops and multiple re-design iterations.

Women-specific risk factors for heart failure: A genetic approach.

PubMed

van der Kemp, Jet; van der Schouw, Yvonne T; Asselbergs, Folkert W; Onland-Moret, N Charlotte

2018-03-01

Heart failure is a complex disease, which is presented differently by men and women. Several studies have shown that reproductive factors, such as age at natural menopause, parity and polycystic ovarian syndrome (PCOS), may play a role in the development of heart failure. Shared genetics may provide clues to underlying mechanisms; however, this has never been examined. Therefore, the aim of the current study was to explore whether any reproductive factor is potentially related to heart failure in women, based on genetic similarities. Conducting a systematic literature review, single nucleotide polymorphisms (SNPs) associated with reproductive factors, heart failure and its risk factors were extracted from recent genome-wide association studies. We tested whether there was any overlap between the SNPs and their proxies of reproductive risk factors with those known for heart failure or its risk factors. In total, 520 genetic variants were found that are associated with reproductive factors, namely age at menarche, age at natural menopause, menstrual cycle length, PCOS, preeclampsia, preterm delivery and spontaneous dizygotic twinning. For heart failure and associated phenotypes, 25 variants were found. Genetic variants for reproductive factors did not overlap with those for heart failure. However, age at menarche, gestational diabetes and PCOS were found to be genetically linked to risk factors for heart failure, such as atrial fibrillation, diabetes and smoking. Corresponding implicated genes, such as TNNI3K, ErbB3, MKL2, MTNR1B and PRKD1, may explain the associations between reproductive factors and heart failure. Exact effector mechanisms of these genes remain to be investigated further. Copyright © 2017. Published by Elsevier B.V.

Congenital heart disease and chromossomopathies detected by the karyotype

PubMed Central

Trevisan, Patrícia; Rosa, Rafael Fabiano M.; Koshiyama, Dayane Bohn; Zen, Tatiana Diehl; Paskulin, Giorgio Adriano; Zen, Paulo Ricardo G.

2014-01-01

OBJECTIVE: To review the relationship between congenital heart defects and chromosomal abnormalities detected by the karyotype. DATA SOURCES: Scientific articles were searched in MEDLINE database, using the descriptors "karyotype" OR "chromosomal" OR "chromosome" AND "heart defects, congenital". The research was limited to articles published in English from 1980 on. DATA SYNTHESIS: Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted in Latin America, in Brazil. It is known that chromosomal abnormalities are frequent, being present in about one in every ten patients with congenital heart disease. Among the karyotype alterations in these patients, the most important is the trisomy 21 (Down syndrome). These patients often have associated extra-cardiac malformations, with a higher risk of morbidity and mortality, which makes heart surgery even more risky. CONCLUSIONS: Despite all the progress made in recent decades in the field of cytogenetic, the karyotype remains an essential tool in order to evaluate patients with congenital heart disease. The detailed dysmorphological physical examination is of great importance to indicate the need of a karyotype. PMID:25119760

Experiences of Patients Living With Heart Failure: A Descriptive Qualitative Study.

PubMed

Seah, Alvin Chuen Wei; Tan, Khoon Kiat; Huang Gan, Juvena Chew; Wang, Wenru

2016-07-01

The purpose of this study was to explore the experiences, needs, and coping strategies of patients living with heart failure in Singapore. A descriptive qualitative design was used. A purposive sample of 15 informants was recruited from two cardiology wards of a tertiary public hospital in Singapore. Individual face-to-face interviews were conducted with a semistructured interview guideline that was developed based on a review of the literature and a pilot study. Content analysis was adopted to analyze the data, and four main categories were identified: perceived causes, manifestations, and prognosis; enduring emotions; managing the condition; and needs from health care professionals. The informants were overwhelmed with the experience of living with heart failure due to the disruptive and uncertain nature of the condition. This study offers health care professionals practical and useful suggestions when providing holistic care for patients with heart failure. © The Author(s) 2015.

Effective heart disease prediction system using data mining techniques.

PubMed

Singh, Poornima; Singh, Sanjay; Pandi-Jain, Gayatri S

2018-01-01

The health care industries collect huge amounts of data that contain some hidden information, which is useful for making effective decisions. For providing appropriate results and making effective decisions on data, some advanced data mining techniques are used. In this study, an effective heart disease prediction system (EHDPS) is developed using neural network for predicting the risk level of heart disease. The system uses 15 medical parameters such as age, sex, blood pressure, cholesterol, and obesity for prediction. The EHDPS predicts the likelihood of patients getting heart disease. It enables significant knowledge, eg, relationships between medical factors related to heart disease and patterns, to be established. We have employed the multilayer perceptron neural network with backpropagation as the training algorithm. The obtained results have illustrated that the designed diagnostic system can effectively predict the risk level of heart diseases.

Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

PubMed

Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

2016-01-01

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. Copyright © 2016 Elsevier Inc. All rights reserved.

Knockout of the Na,K-ATPase α2-isoform in cardiac myocytes delays pressure overload-induced cardiac dysfunction

PubMed Central

Rindler, Tara N.; Lasko, Valerie M.; Nieman, Michelle L.; Okada, Motoi; Lorenz, John N.

2013-01-01

The α2-isoform of the Na,K-ATPase (α2) is the minor isoform of the Na,K-ATPase expressed in the cardiovascular system and is thought to play a critical role in the regulation of cardiovascular hemodynamics. However, the organ system/cell type expressing α2 that is required for this regulation has not been fully defined. The present study uses a heart-specific knockout of α2 to further define the tissue-specific role of α2 in the regulation of cardiovascular hemodynamics. To accomplish this, we developed a mouse model using the Cre/loxP system to generate a tissue-specific knockout of α2 in the heart using β-myosin heavy chain Cre. We have achieved a 90% knockout of α2 expression in the heart of the knockout mice. Interestingly, the heart-specific knockout mice exhibit normal basal cardiac function and systolic blood pressure, and in addition, these mice develop ACTH-induced hypertension in response to ACTH treatment similar to control mice. Surprisingly, the heart-specific knockout mice display delayed onset of cardiac dysfunction compared with control mice in response to pressure overload induced by transverse aortic constriction; however, the heart-specific knockout mice deteriorated to control levels by 9 wk post-transverse aortic constriction. These results suggest that heart expression of α2 does not play a role in the regulation of basal cardiovascular function or blood pressure; however, heart expression of α2 plays a role in the hypertrophic response to pressure overload. This study further emphasizes that the tissue localization of α2 determines its unique roles in the regulation of cardiovascular function. PMID:23436327

Changing Landscape of Congenital Heart Disease.

PubMed

Bouma, Berto J; Mulder, Barbara J M

2017-03-17

Congenital heart disease is the most frequently occurring congenital disorder affecting ≈0.8% of live births. Thanks to great efforts and technical improvements, including the development of cardiopulmonary bypass in the 1950s, large-scale repair in these patients became possible, with subsequent dramatic reduction in morbidity and mortality. The ongoing search for progress and the growing understanding of the cardiovascular system and its pathophysiology refined all aspects of care for these patients. As a consequence, survival further increased over the past decades, and a new group of patients, those who survived congenital heart disease into adulthood, emerged. However, a large range of complications raised at the horizon as arrhythmias, endocarditis, pulmonary hypertension, and heart failure, and the need for additional treatment became clear. Technical solutions were sought in perfection and creation of new surgical techniques by developing catheter-based interventions, with elimination of open heart surgery and new electronic devices enabling, for example, multisite pacing and implantation of internal cardiac defibrillators to prevent sudden death. Over time, many pharmaceutical studies were conducted, changing clinical treatment slowly toward evidence-based care, although results were often limited by low numbers and clinical heterogeneity. More attention has been given to secondary issues like sports participation, pregnancy, work, and social-related difficulties. The relevance of these issues was already recognized in the 1970s when the need for specialized centers with multidisciplinary teams was proclaimed. Finally, research has become incorporated in care. Results of intervention studies and registries increased the knowledge on epidemiology of adults with congenital heart disease and their complications during life, and at the end, several guidelines became easily accessible, guiding physicians to deliver care appropriately. Over the past decades, the landscape of adult congenital heart disease has changed dramatically, which has to be continued in the future. © 2017 American Heart Association, Inc.

Overlapping and opposing functions of G protein-coupled receptor kinase 2 (GRK2) and GRK5 during heart development.

PubMed

Philipp, Melanie; Berger, Ina M; Just, Steffen; Caron, Marc G

2014-09-19

G protein-coupled receptor kinases 2 (GRK2) and 5 (GRK5) are fundamental regulators of cardiac performance in adults but are less well characterized for their function in the hearts of embryos. GRK2 and -5 belong to different subfamilies and function as competitors in the control of certain receptors and signaling pathways. In this study, we used zebrafish to investigate whether the fish homologs of GRK2 and -5, Grk2/3 and Grk5, also have unique, complementary, or competitive roles during heart development. We found that they differentially regulate the heart rate of early embryos and equally facilitate heart function in older embryos and that both are required to develop proper cardiac morphology. A loss of Grk2/3 results in dilated atria and hypoplastic ventricles, and the hearts of embryos depleted in Grk5 present with a generalized atrophy. This Grk5 morphant phenotype was associated with an overall decrease of early cardiac progenitors as well as a reduction in the area occupied by myocardial progenitor cells. In the case of Grk2/3, the progenitor decrease was confined to a subset of precursor cells with a committed ventricular fate. We attempted to rescue the GRK loss-of-function heart phenotypes by downstream activation of Hedgehog signaling. The Grk2/3 loss-of-function embryos were rescued by this approach, but Grk5 embryos failed to respond. In summary, we found that GRK2 and GRK5 control cardiac function as well as morphogenesis during development although with different morphological outcomes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Humoral immunity in heart failure.

PubMed

Sarkar, Amrita; Rafiq, Khadija

2018-05-17

Cardiovascular disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including: hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to heart failure (HF). There are several treatments available all over the world, but still CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential, and may suggest potential new treatment strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effectiveness of the Complete Health Improvement Program

ERIC Educational Resources Information Center

Hutchins, Mathew; Melancon, Jim; Sneed, Demarcus; Nunning, Jennifer

2015-01-01

Currently, heart disease and diabetes dominate society as the leading cause of death for Americans. In this study, we examined the effectiveness of a lifestyle enhancement program on factors related to the development of heart disease. The Wabash Valley Complete Health Improvement Program (CHIP) is a community-based lifestyle change program with…

Barriers to Fruit and Vegetable Intake among College Students

ERIC Educational Resources Information Center

Samples, Evangeline Yvonne

2017-01-01

Numerous studies suggest that most college students consume inadequate amounts of fruits and vegetables. In turn, such poor dietary habits predispose collegians to develop obesity, heart disease, and diabetes. Fruit and vegetable intake provides psychological benefits throughout the lifespan; reduces the risks for heart disease, stroke, and…

Novel insights into the development of chagasic cardiomyopathy: role of PI3Kinase/NO axis.

PubMed

Roman-Campos, Danilo; Sales-Junior, Policarpo; Duarte, Hugo L; Gomes, Enéas R; Lara, Aline; Campos, Paula; Rocha, Nazareth N; Resende, Rodrigo R; Ferreira, Anderson; Guatimosim, Sílvia; Gazzinelli, Ricardo T; Ropert, Catherine; Cruz, Jader S

2013-09-10

Chagas' disease is one of the leading causes of heart failure in Latin American countries. Despite its great social impact, there is no direct evidence in the literature explaining the development of heart failure in Chagas' disease. Therefore, the main objective of the study was to investigate the development of the Chagas' disease towards its chronic phase and correlate with modifications in the cellular electrophysiological characteristics of the infected heart. Using a murine model of Chagas' disease, we confirmed and extended previous findings of altered electrocardiogram and echocardiogram in this cardiomyopathy. The observed changes in the electrocardiogram were correlated with the prolonged action potential and reduced transient outward potassium current density. Reduced heart function was associated with remodeling of intracellular calcium handling, altered extracellular matrix content, and to a set of proteins involved in the control of cellular contractility in ventricular myocytes. Furthermore, disruption of calcium homeostasis was partially due to activation of the PI3Kinase/nitric oxide signaling pathway. Finally, we propose a causal link between the inflammatory mediators and heart remodeling during chagasic cardiomyopathy. Altogether our results demonstrate that heart failure in Chagas' disease may occur due to electrical and mechanical remodeling of cardiac myocytes, and suggest that AKT/PI3K/NO axis could be an important pharmacological target to improve the disease outcome. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Psychological Perspectives on the Development of Coronary Heart Disease

ERIC Educational Resources Information Center

Matthews, Karen A.

2005-01-01

Psychological science has new opportunities to have major input into the understanding of the development of coronary heart disease. This article provides an overview of advances in understanding the etiology of heart disease, recently applied technologies for measuring early stages of heart disease, and an accumulating base of evidence on the…

Development of a Comprehensive Heart Disease Knowledge Questionnaire

ERIC Educational Resources Information Center

Bergman, Hannah E.; Reeve, Bryce B.; Moser, Richard P.; Scholl, Sarah; Klein, William M. P.

2011-01-01

Background: Heart disease is the number one killer of both men and women in the United States, yet a comprehensive and evidence-based heart disease knowledge assessment is currently not available. Purpose: This paper describes the two-phase development of a novel heart disease knowledge questionnaire. Methods: After review and critique of the…

Abnormal brain development in newborns with congenital heart disease.

PubMed

Miller, Steven P; McQuillen, Patrick S; Hamrick, Shannon; Xu, Duan; Glidden, David V; Charlton, Natalie; Karl, Tom; Azakie, Anthony; Ferriero, Donna M; Barkovich, A James; Vigneron, Daniel B

2007-11-08

Congenital heart disease in newborns is associated with global impairment in development. We characterized brain metabolism and microstructure, as measures of brain maturation, in newborns with congenital heart disease before they underwent heart surgery. We studied 41 term newborns with congenital heart disease--29 who had transposition of the great arteries and 12 who had single-ventricle physiology--with the use of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before cardiac surgery. We calculated the ratio of N-acetylaspartate to choline (which increases with brain maturation), the ratio of lactate to choline (which decreases with maturation), average diffusivity (which decreases with maturation), and fractional anisotropy of white-matter tracts (which increases with maturation). We compared these findings with those in 16 control newborns of a similar gestational age. As compared with control newborns, those with congenital heart disease had a decrease of 10% in the ratio of N-acetylaspartate to choline (P=0.003), an increase of 28% in the ratio of lactate to choline (P=0.08), an increase of 4% in average diffusivity (P<0.001), and a decrease of 12% in white-matter fractional anisotropy (P<0.001). Preoperative brain injury, as seen on MRI, was not significantly associated with findings on MRS or DTI. White-matter injury was observed in 13 newborns with congenital heart disease (32%) and in no control newborns. Term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery. The imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero. Copyright 2007 Massachusetts Medical Society.

Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy

PubMed Central

Dees, Ellen; Miller, Paul M.; Moynihan, Katherine L.; Pooley, Ryan D.; Hunt, R. Pierre; Galindo, Cristi L.; Rottman, Jeffrey N.; Bader, David M.

2012-01-01

SUMMARY CENP-F is a large multifunctional protein with demonstrated regulatory roles in cell proliferation, vesicular transport and cell shape through its association with the microtubule (MT) network. Until now, analysis of CENP-F has been limited to in vitro analysis. Here, using a Cre-loxP system, we report the in vivo disruption of CENP-F gene function in murine cardiomyocytes, a cell type displaying high levels of CENP-F expression. Loss of CENP-F function in developing myocytes leads to decreased cell division, blunting of trabeculation and an initially smaller, thin-walled heart. Still, embryos are born at predicted mendelian ratios on an outbred background. After birth, hearts lacking CENP-F display disruption of their intercalated discs and loss of MT integrity particularly at the costamere; these two structures are essential for cell coupling/electrical conduction and force transduction in the heart. Inhibition of myocyte proliferation and cell coupling as well as loss of MT maintenance is consistent with previous reports of generalized CENP-F function in isolated cells. One hundred percent of these animals develop progressive dilated cardiomyopathy with heart block and scarring, and there is a 20% mortality rate. Importantly, although it has long been postulated that the MT cytoskeleton plays a role in the development of heart disease, this study is the first to reveal a direct genetic link between disruption of this network and cardiomyopathy. Finally, this study has broad implications for development and disease because CENP-F loss of function affects a diverse array of cell-type-specific activities in other organs. PMID:22563055

Defective support network: a major obstacle to coping for patients with heart failure: a qualitative study

PubMed Central

Shahrbabaki, Parvin Mangolian; Nouhi, Esmat; Kazemi, Majid; Ahmadi, Fazlollah

2016-01-01

Background Heart failure as a chronic disease poses many challenges for a patient in his or her everyday life. Support in various aspects of life positively affects coping strategies and influences the well-being and health outcomes of heart failure patients. Inadequate support may lead to a worsening of symptoms, increased hospital readmissions, psychological disorders, and a reduced quality of life. Objective This study explored obstacles to coping related to support for heart failure patients as viewed by the patients themselves and their family members and caregivers. Design This qualitative study was conducted using content analysis. The 20 Iranian participants included 11 patients with heart failure, three cardiologists, three nurses, and three family members of heart failure patients selected through purposive sampling. Data were collected through semi-structured interviews and analyzed using the Lundman and Graneheim qualitative content analysis method. Results During data analysis, ‘defective support network’ developed as the main theme along with four other categories of ‘inadequate family performance’, ‘inadequate support by the healthcare team’, ‘distorted societal social support’, and ‘inadequate welfare support’. Conclusion The findings of the current study can assist health authorities and planners in identifying the needs of patients with heart failure so as to focus and plan on facilitating their coping as much as possible by obviating the existing obstacles. PMID:27041539

A randomised, simulated study assessing auscultation of heart rate at birth.

PubMed

Voogdt, Kevin G J A; Morrison, Allison C; Wood, Fiona E; van Elburg, Ruurd M; Wyllie, Jonathan P

2010-08-01

Heart rate is a primary clinical indicator directing newborn resuscitation. The time taken to assess the heart rate by auscultation in relation to accuracy during newborn resuscitation is not known. To assess both the accuracy and time taken to assess heart rate by stethoscope in simulated resuscitation scenarios. The VitalSim((c)) manikin (Laerdal Medical, Stavanger, Norway) was used in this randomised, single blind study. Four heart rate settings (0, 40, 80, 120 beats per minute (bpm)) were randomly assigned. Participants assessed them by auscultation in three different scenarios. The first scenario was to assess the actual heart rate at birth. In the second scenario, heart rate was assessed during ventilation and assigned to standard ranges (<60, 60-100, >100bpm). In the third scenario, heart rate was assessed after three cycles of compressions and ventilation and assigned to standard ranges. In total 61 midwives, nurses and doctors performed 183 assessments. Mean time to estimate heart rate for scenarios 1, 2 and 3 was: 17.0, 9.8 and 7.8s respectively. Heart rate assessments were inaccurate in 31% (scenario 1), 28% (scenarios 2) and 26% (scenario 3). There was a trend for assessors who were accurate to be quicker and this achieved significance in scenario 2 (p<0.02). Inaccurate assessment would have made a difference to management in 28% of all cases. Mean time to estimate heart rate for the scenarios varied between 7.8 and 17.0s. Twenty-eight percent of all heart rate assessments would have prompted incorrect management during resuscitation or stabilization. Of incorrect assessments, 73% were overestimations. Further research is required to develop a rapid and accurate method for determining heart rate during newborn resuscitation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Kennedy Space Center Coronary Heart Disease Risk Screening Program

NASA Technical Reports Server (NTRS)

Tipton, David A.; Scarpa, Philip J.

1999-01-01

Coronary heart disease (CHD) is the number one cause of death in the U.S. It is a likely cause of death and disability in the lives of employees at Kennedy Space Center (KSC) as well. The KSC Biomedical Office used a multifactorial formula developed by the Framingham Heart Study to calculate CHD risk probabilities for individuals in a segment of the KSC population who require medical evaluation for job certification. Those individuals assessed to have a high risk probability will be targeted for intervention.

New Stethoscope With Extensible Diaphragm.

PubMed

Takashina, Tsunekazu; Shimizu, Masashi; Muratake, Torakazu; Mayuzumi, Syuichi

2016-08-25

This study compared the diagnostic efficacy of the common suspended diaphragm stethoscope (SDS) with a new extensible diaphragm stethoscope (EDS) for low-frequency heart sounds. The EDS was developed by using an ethylene propylene diene monomer diaphragm. The results showed that the EDS enhanced both the volume and quality of low-frequency heart sounds, and improved the ability of examiners to auscultate such heart sounds. Based on the results of the sound analysis, the EDS is more efficient than the SDS. (Circ J 2016; 80: 2047-2049).

Management of BB shot wounds to the heart.

PubMed

Thompson, E C; Block, E F; Mancini, M C

1996-01-01

The aim of this study was to review our experience with BB shot injuries to the heart. This is a retrospective chart review. Three patients were found to have BB injuries to the heart. All patients were stable upon presentation. Echocardiography localized the BB pellets to the muscular septum. All patients were treated with nonoperative therapy. There was not mortality. One patient developed an interventricular conduction delay that resolved before discharge. Nonoperative management of stable patients who present with BB wounds to the heart is safe and effective if the BB is intramuscular. An echocardiogram should be used to localize the pellets and evaluate the pericardium.

[Motor protein Kinesin-6 and ischemic heart disease].

PubMed

Koroleva, O S; Zateĭshchikov, D A

2010-01-01

The review describes possible role of kinesins in development of coronary heart disease and efficacy of treatment with statins. Fourty five kinesins are represented in human body making up a superfamily of universal and simplest motor proteins which are expressed almost in all tissues. Level of kinesin 6 is 5% higher than expression of other kinesins in some segments of coronary arteries and it is relatively low in organs playing unknown role in susceptibility to atherosclerosis. As a result of several genoms wide association studies the role of polymorphic marker Thr719Arg of kinesin 6 gene in development of ischemic heart disease, myocardial infarction, and in efficacy of therapy with statins was revealed.

SDOCT Doppler velocimetry for investigating the morphological influences on blood flow in the developing chick embryo heart

NASA Astrophysics Data System (ADS)

Davis, Anjul M.; Rothenberg, Florence G.; Law, Tzuo H.; Taber, Larry A.; Izatt, Joseph A.

2007-02-01

The onset of congenital heart disease (CHD) is believed to occur at very early stages of development. Investigations in the initiation and development of CHD has been hampered by the inability to image early stage heart structure and function, in vivo. Imaging small animals using optical coherence tomography (OCT) has filled a niche between the limited penetration depth of confocal microscopy and insufficient resolution from ultrasound. Previous demonstrations of chick heart imaging using OCT have entailed excision of, or arresting the heart to prevent motion artifacts. In this summary, we introduce SDOCT Doppler velocimetry as an enhancement of Doppler OCT for in vivo measurement of localized temporal blood flow dynamics. With this technique, dynamic velocity waveforms were measured in the outflow tract of the heart tube. These flow dynamics correlate to a finite element model of pulsatile flow and may lead to a further understanding of morphological influences on early heart development.

An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation.

PubMed

Chen, Xiong; Yu, Weihui; Li, Weixin; Zhang, Hailing; Huang, Weijian; Wang, Jingying; Zhu, Weiwei; Fang, Qilu; Chen, Chao; Li, Xiaokun; Liang, Guang

2018-01-01

Obesity is a growing pandemic in both developed and developing countries. Lipid overload in obesity generates a chronic, low-grade inflammation state. Increased inflammation in heart and renal tissues has been shown to promote the progression of heart and renal damage in obesity. Previously, we found that a novel chalcone derivative, L6H21, inhibited lipopolysaccharide-induced inflammatory response. In the present study, we investigated the effects of L6H21 on inflammatory responses in culture and in animal models of lipid overload. We utilized palmitic acid (PA) challenging in mouse peritoneal macrophages and apolipoprotein E knockout (ApoE -/- ) mice fed a high fat diet (HFD) to study whether L6H21 mitigates the inflammatory response. Our studies show that L6H21 significantly reduced PA-induced expression of inflammatory cytokines in macrophages by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NFκB) signaling pathways. L6H21 also reduced fibrosis in the kidney and heart tissues, and indices of inflammatory response in the ApoE -/- mice fed a HFD. These effects in vivo were also associated with inhibition of MAPK and NFκB signaling by L6H21. These findings strongly suggest that L6H21 may be a potential agent for high fat diet-induced injuries in heart and kidney. Copyright © 2017. Published by Elsevier Inc.

Development of measures of organizational leadership for health promotion.

PubMed

Barrett, Linda; Plotnikoff, Ronald C; Raine, Kim; Anderson, Donna

2005-04-01

This study describes the development and psychometric evaluation of four scales measuring leadership for health promotion at an organizational level in the baseline survey (n=144) of the Alberta Heart Health Project. Content validity was established through a series of focus groups and expert opinion appraisals, pilot testing of a draft based on capacity assessment instruments developed by other provinces involved in the Canadian Heart Health Initiative, and the literature. Psychometric analyses provided empirical evidence of the construct validity and reliability of the organizational leadership scales. Principal component analysis verified the unidimensionality of the leadership scales of (a) Practices for Organizational Learning, (b) Wellness Planning, (c) Workplace Climate, and (d) Organization Member Development. Scale alpha coefficients ranged between .79 and .91 thus establishing good to high scale internal consistencies. These measures can be used by both researchers and practitioners for the assessment of organizational leadership for health promotion and heart health promotion.

Can Vitamins Help Prevent a Heart Attack?

MedlinePlus

... taking vitamins help prevent heart disease or a heart attack? Answers from Rekha Mankad, M.D. It's not yet clear ... risk of developing heart disease or having a heart attack. But, what is known is that no vitamin ...

Changes in Heart Rate Associated with Exenatide Once Weekly: Pooled Analysis of Clinical Data in Patients with Type 2 Diabetes.

PubMed

Marso, Steven P; Hardy, Elise; Han, Jenny; Wang, Hui; Chilton, Robert J

2018-04-01

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and - 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = - 0.3 to - 0.4). Baseline heart rate was the strongest predictor of increased heart rate. Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.

Lumican Deficiency Results In Cardiomyocyte Hypertrophy With Altered Collagen Assembly

PubMed Central

Dupuis, Loren E.; Berger, Matthew G.; Feldman, Samuel; Doucette, Lorna; Fowlkes, Vennece; Chakravarti, Shukti; Thibaudeau, Sarah; Alcala, Nicolas E.; Bradshaw, Amy D.; Kern, Christine B.

2015-01-01

The ability of the heart to adapt to increased stress is dependent on modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest LUM deficient mice (lum−/−) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum−/− hearts have not been evaluated. These studies show LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum−/− neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum−/− hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum−/− hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagenα1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum−/− hearts. There was also a reduction in the β and γ forms of collagenα1(I) in lum−/− hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum−/− hearts, indicating LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate multiple factors of collagen assembly in the murine heart. Further investigation into the role of LUM may yield novel therapeutic targets and/or biomarkers for patients with cardiovascular disease. PMID:25886697

Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation.

PubMed

Cole, Robert Townsend; Gandhi, Jonathan; Bray, Robert A; Gebel, Howard M; Yin, Michael; Shekiladze, Nikolaz; Young, An; Grant, Aubrey; Mahoney, Ian; Laskar, S Raja; Gupta, Divya; Bhatt, Kunal; Book, Wendy; Smith, Andrew; Nguyen, Duc; Vega, J David; Morris, Alanna A

2018-04-01

Despite improvements in outcomes after heart transplantation, black recipients have worse survival compared with non-black recipients. The source of such disparate outcomes remains largely unknown. We hypothesize that a propensity to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody-mediated rejection (AMR) may account for racial differences in sub-optimal outcomes after heart transplant. In this study we aimed to determine the role of dnDSA and AMR in racial disparities in post-transplant outcomes. This study was a single-center, retrospective analysis of 137 heart transplant recipients (81% male, 48% black) discharged from Emory University Hospital. Patients were classified as black vs non-black for the purpose of our analysis. Kaplan-Meier and Cox regression analyses were used to evaluate the association between race and selected outcomes. The primary outcome was the development of dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft dysfunction or death. After 3.7 years of follow-up, 39 (28.5%) patients developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models, black race was associated with a higher risk of developing dnDSA (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non-black race. Black race was also associated with a higher risk of all-cause graft dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p = 0.044). However, in a multivariable model incorporating dnDSA, black race was no longer a significant risk factor. Only dnDSA development was significantly associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to 12.44, p = 0.001). Black transplant recipients are at higher risk for the development of dnDSA and treated AMR, which may account for racial disparities in outcomes after heart transplantation. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Heart Performance Determination by Visualization in Larval Fishes: Influence of Alternative Models for Heart Shape and Volume

PubMed Central

Perrichon, Prescilla; Grosell, Martin; Burggren, Warren W.

2017-01-01

Understanding cardiac function in developing larval fishes is crucial for assessing their physiological condition and overall health. Cardiac output measurements in transparent fish larvae and other vertebrates have long been made by analyzing videos of the beating heart, and modeling this structure using a conventional simple prolate spheroid shape model. However, the larval fish heart changes shape during early development and subsequent maturation, but no consideration has been made of the effect of different heart geometries on cardiac output estimation. The present study assessed the validity of three different heart models (the “standard” prolate spheroid model as well as a cylinder and cone tip + cylinder model) applied to digital images of complete cardiac cycles in larval mahi-mahi and red drum. The inherent error of each model was determined to allow for more precise calculation of stroke volume and cardiac output. The conventional prolate spheroid and cone tip + cylinder models yielded significantly different stroke volume values at 56 hpf in red drum and from 56 to 104 hpf in mahi. End-diastolic and stroke volumes modeled by just a simple cylinder shape were 30–50% higher compared to the conventional prolate spheroid. However, when these values of stroke volume multiplied by heart rate to calculate cardiac output, no significant differences between models emerged because of considerable variability in heart rate. Essentially, the conventional prolate spheroid shape model provides the simplest measurement with lowest variability of stroke volume and cardiac output. However, assessment of heart function—especially if stroke volume is the focus of the study—should consider larval heart shape, with different models being applied on a species-by-species and developmental stage-by-stage basis for best estimation of cardiac output. PMID:28725199

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.

Epidemiology of coronary heart disease: the Puerto Rico heart health program revisted.

PubMed

García-Palmieri, Mario R

2013-01-01

Coronary heart disease (CHD) remains as the main cause of death in most countries of the world including Puerto Rico. Due to the importance of gathering knowledge regarding the harmful effects and risk factors associated with the development of CHD some basic information is reviewed to stimulate the institution of measures for reduction of the prevalence of clinical CHD and its ultimate consequences. Special attention is given in the manuscript of the Puerto Rico Heart Health Program conducted in men aged 45-64 residing in four rural and three urban areas. The Puerto Rico and the Honolulu Study confirmed the initial publication on the epidemiology of coronary heart disease by the Framingham study. The presentation of some data collected among the three studies strengthen the message of avoiding the development of CHD by installing preventive measures for control and reduction of the risk factors. Concurrent data obtained in the three studies is presented. Although the degree of the involvement of the populations is higher in Framingham than in Puerto Rico and Honolulu, the deleterious effects of specific risk factors are harmful in all the three populations. Difference in the prevalence of risk factors among the urban and rural males in Puerto Rico is also illustrated. It is our hope that more intense measures be instituted in Puerto Rico at all levels in order to control risk factors and reduce the incidence of coronary disease in Puerto Rico.

Development of an anaerobic threshold (HRLT, HRVT) estimation equation using the heart rate threshold (HRT) during the treadmill incremental exercise test

PubMed Central

Ham, Joo-ho; Park, Hun-Young; Kim, Youn-ho; Bae, Sang-kon; Ko, Byung-hoon

2017-01-01

[Purpose] The purpose of this study was to develop a regression model to estimate the heart rate at the lactate threshold (HRLT) and the heart rate at the ventilatory threshold (HRVT) using the heart rate threshold (HRT), and to test the validity of the regression model. [Methods] We performed a graded exercise test with a treadmill in 220 normal individuals (men: 112, women: 108) aged 20–59 years. HRT, HRLT, and HRVT were measured in all subjects. A regression model was developed to estimate HRLT and HRVT using HRT with 70% of the data (men: 79, women: 76) through randomization (7:3), with the Bernoulli trial. The validity of the regression model developed with the remaining 30% of the data (men: 33, women: 32) was also examined. [Results] Based on the regression coefficient, we found that the independent variable HRT was a significant variable in all regression models. The adjusted R2 of the developed regression models averaged about 70%, and the standard error of estimation of the validity test results was 11 bpm, which is similar to that of the developed model. [Conclusion] These results suggest that HRT is a useful parameter for predicting HRLT and HRVT. PMID:29036765

Development of an anaerobic threshold (HRLT, HRVT) estimation equation using the heart rate threshold (HRT) during the treadmill incremental exercise test.

PubMed

Ham, Joo-Ho; Park, Hun-Young; Kim, Youn-Ho; Bae, Sang-Kon; Ko, Byung-Hoon; Nam, Sang-Seok

2017-09-30

The purpose of this study was to develop a regression model to estimate the heart rate at the lactate threshold (HRLT) and the heart rate at the ventilatory threshold (HRVT) using the heart rate threshold (HRT), and to test the validity of the regression model. We performed a graded exercise test with a treadmill in 220 normal individuals (men: 112, women: 108) aged 20-59 years. HRT, HRLT, and HRVT were measured in all subjects. A regression model was developed to estimate HRLT and HRVT using HRT with 70% of the data (men: 79, women: 76) through randomization (7:3), with the Bernoulli trial. The validity of the regression model developed with the remaining 30% of the data (men: 33, women: 32) was also examined. Based on the regression coefficient, we found that the independent variable HRT was a significant variable in all regression models. The adjusted R2 of the developed regression models averaged about 70%, and the standard error of estimation of the validity test results was 11 bpm, which is similar to that of the developed model. These results suggest that HRT is a useful parameter for predicting HRLT and HRVT. ©2017 The Korean Society for Exercise Nutrition

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.

Bidirectional Fusion of the Heart-forming Fields in the Developing Chick Embryo

PubMed Central

Moreno-Rodriguez, R.A.; Krug, E.L.; Reyes, L.; Villavicencio, L.; Mjaatvedt, C.H.; Markwald, R.R.

2007-01-01

It is generally thought that the early pre-tubular chick heart is formed by fusion of the anterior or cephalic limits of the paired cardiogenic fields. However, this study shows that the heart fields initially fuse at their midpoint to form a transitory “butterfly”-shaped, cardiogenic structure. Fusion then progresses bi-directionally along the longitudinal axis in both cranial and caudal directions. Using in vivo labeling, we demonstrate that cells along the ventral fusion line are highly motile, crossing future primitive segments. We found that mesoderm cells migrated cephalically from the unfused tips of the anterior/cephalic wings into the head mesenchyme in the region that has been called the secondary heart field. Perturbing the anterior/cranial fusion results in formation of a biconal heart. A theoretical role of the ventral fusion line acting as a “heart organizer” and its role in cardia bifida is discussed. PMID:16252277

The impact of high-salt exposure on cardiovascular development in the early chick embryo.

PubMed

Wang, Guang; Zhang, Nuan; Wei, Yi-Fan; Jin, Yi-Mei; Zhang, Shi-Yao; Cheng, Xin; Ma, Zheng-Lai; Zhao, Shu-Zhu; Chen, You-Peng; Chuai, Manli; Hocher, Berthold; Yang, Xuesong

2015-11-01

In this study, we show that high-salt exposure dramatically increases chick mortality during embryo development. As embryonic mortality at early stages mainly results from defects in cardiovascular development, we focused on heart formation and angiogenesis. We found that high-salt exposure enhanced the risk of abnormal heart tube looping and blood congestion in the heart chamber. In the presence of high salt, both ventricular cell proliferation and apoptosis increased. The high osmolarity induced by high salt in the ventricular cardiomyocytes resulted in incomplete differentiation, which might be due to reduced expression of Nkx2.5 and GATA4. Blood vessel density and diameter were suppressed by exposure to high salt in both the yolk sac membrane (YSM) and chorioallantoic membrane models. In addition, high-salt-induced suppression of angiogenesis occurred even at the vasculogenesis stage, as blood island formation was also inhibited by high-salt exposure. At the same time, cell proliferation was repressed and cell apoptosis was enhanced by high-salt exposure in YSM tissue. Moreover, the reduction in expression of HIF2 and FGF2 genes might cause high-salt-suppressed angiogenesis. Interestingly, we show that high-salt exposure causes excess generation of reactive oxygen species (ROS) in the heart and YSM tissues, which could be partially rescued through the addition of antioxidants. In total, our study suggests that excess generation of ROS might play an important role in high-salt-induced defects in heart and angiogenesis. © 2015. Published by The Company of Biologists Ltd.

Comparison of early period results of blood use in open heart surgery.

PubMed

Huseyin, Serhat; Yuksel, Volkan; Guclu, Orkut; Turan, Fatma Nesrin; Canbaz, Suat; Ege, Turan; Sunar, Hasan

2016-01-01

Various adverse effects of homologous blood transfusion detected particularly in open heart surgery, in which it is frequently used, lead researchers to study on autologous blood use and to evaluate the patient's blood better. Due to the complications of homologous blood transfusion, development of techniques that utilize less transfusion has become inevitable. We aimed to evaluate the effects of acute normovolemic hemodilution (ANH) in patients undergoing open heart surgery. In this study, 120 patients who underwent open heart surgery were included. Patients were grouped into three: Autologous transfusion group (Group 1), homologous transfusion group (Group 2), and those received autologous blood and homologous blood products (Group 3). Patient data regarding preoperative characteristics, biochemical parameters, drainage, extubation time, duration of stay at intensive care, atrial fibrillation (AF) development, and hospital stay were recorded. A statistically significant difference ( P < 0.005) was found in favor of autologous group (Group 1) with respect to gender, body surface area, European System for Cardiac Operative Risk Evaluation, smoking, hematocrit levels, platelet counts, urea, C-reactive protein levels, protamine use, postoperative drainage, frequency of AF development, intubation period, stay at intensive care and hospital stay, and amount of used blood products. The use of autologous blood rather than homologous transfusion is not only attenuates side effects and complications of transfusion but also positively affects postoperative recovery process. Therefore, ANH can be considered as an easy, effective, and cheap technique during open heart surgery.

A new paradigm for obtaining marketing approval for pediatric-sized prosthetic heart valves.

PubMed

Yoganathan, Ajit P; Fogel, Mark; Gamble, Susan; Morton, Michael; Schmidt, Paul; Secunda, Jeff; Vidmar, Sara; Del Nido, Pedro

2013-10-01

Congenital heart valve disease is one of the most common abnormalities in children. There are limited technological solutions available for treating children with congenital heart valve diseases. The aim of this study is to provide the details of the consensus reached in terms of pediatric definitions, design approach, in vitro testing, and clinical trials, which may be used as guidance for developing prosthetic heart valves for the pediatric indication. In stark contrast to the various designs of adult-sized replacement valves available in the market, there are no Food and Drug Administration (FDA)-approved prosthetic heart valves available for use in the pediatric population. There is a pressing need for FDA-approved pediatric valve devices in the United States. The pediatric patient population has been typically excluded from replacement heart valve trials for several reasons. In January 2010, heart valve manufacturers and pediatric clinicians collaborated with academicians and FDA staff in a workshop to suggest ways to successfully evaluate pediatric prosthetic valves and conduct pediatric clinical trials to provide acceptable heart valve replacement options for this patient population. Recommendations, derived from ISO 5840:2005 and the 2010 FDA Draft Replacement Heart Valve Guidance, are provided for hydrodynamic, durability, and fatigue testing. The article specifically addresses in vitro and premarket and postmarket approval clinical studies that should be considered by a heart valve manufacturer for obtaining regulatory approval of pediatric sizes of prosthetic heart valve designs that are already approved for adult clinical use. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Measuring the effects of massage on exercise performance and cardiopulmonary response in children with and without heart disease: a pilot study.

PubMed

Beider, Shay; Boulanger, Karen T; Joshi, Milind; Pan, Yann Ping; Chang, Ruey-Kang R

2010-09-28

Congenital heart disease, a common and serious birth defect, affects 8 per 1000 live-born infants. Decreased exercise capacity and development of obesity is common in this population. These children may benefit from therapies, such as massage therapy, that could enhance cardiovascular and skeletal muscle function when they exercise. A pilot study conducted at the pediatric cardiology clinic of the Mattel Children's Hospital of the University of California-Los Angeles examined the safety and feasibility of measuring the effects of pre-exercise massage on exercise performance and cardiopulmonary response in children with and without heart disease. SIXTEEN CHILDREN (MEAN AGE: 9.2 ± 2.2 years) participated in the study. Ten participants had various forms of heart disease, and six children were healthy. A female certified massage therapist with specialized training in pediatric massage provided a 30-minute massage to the participants. Using a standard protocol, each participant underwent two exercise tests: one test with and one without pre-exercise massage. Heart rate, blood pressure, and oxygen uptake (VO(2)) were measured in the participants. All recruited participants completed the study. No adverse events occurred during any of the exercise tests or massage sessions. Measurements during exercise with or without a preceding massage were compared, and the pre-exercise massage condition yielded a significantly higher heart rate and higher minute ventilation. Measurements during exercise in children with heart disease and in healthy participants showed no significant differences in peak heart rate, blood pressure, peak VO(2), peak work rate, minute ventilation, or respiratory quotient. In this study, peak heart rate, peak VO(2), and peak minute ventilation were higher when children received a massage before exercise testing. Larger studies will be needed to investigate the strength of this finding. Future studies should include measurements of anxiety and psychological factors in addition to cardiopulmonary measures.

Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

PubMed Central

Cai, Wenxuan; Tucholski, Trisha M.; Gregorich, Zachery R.; Ge, Ying

2016-01-01

Introduction Diseases of the heart are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood. Areas covered Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets. PMID:27448560

"String theory" of c-kit(pos) cardiac cells: a new paradigm regarding the nature of these cells that may reconcile apparently discrepant results.

PubMed

Keith, Matthew C L; Bolli, Roberto

2015-03-27

Although numerous preclinical investigations have consistently demonstrated salubrious effects of c-kit(pos) cardiac cells administered after myocardial infarction, the mechanism of action remains highly controversial. We and others have found little or no evidence that these cells differentiate into mature functional cardiomyocytes, suggesting paracrine effects. In this review, we propose a new paradigm predicated on a comprehensive analysis of the literature, including studies of cardiac development; we have (facetiously) dubbed this conceptual construct "string theory" of c-kit(pos) cardiac cells because it reconciles multifarious and sometimes apparently discrepant results. There is strong evidence that, during development, the c-kit receptor is expressed in different pools of cardiac progenitors (some capable of robust cardiomyogenesis and others with little or no contribution to myocytes). Accordingly, c-kit positivity, in itself, does not define the embryonic origins, lineage capabilities, or differentiation capacities of specific cardiac progenitors. C-kit(pos) cells derived from the first heart field exhibit cardiomyogenic potential during development, but these cells are likely depleted shortly before or after birth. The residual c-kit(pos) cells found in the adult heart are probably of proepicardial origin, possess a mesenchymal phenotype (resembling bone marrow mesenchymal stem/stromal cells), and are capable of contributing significantly only to nonmyocytic lineages (fibroblasts, smooth muscle cells, and endothelial cells). If these 2 populations (first heart field and proepicardium) express different levels of c-kit, the cardiomyogenic potential of first heart field progenitors might be reconciled with recent results of c-kit(pos) cell lineage tracing studies. The concept that c-kit expression in the adult heart identifies epicardium-derived, noncardiomyogenic precursors with a mesenchymal phenotype helps to explain the beneficial effects of c-kit(pos) cell administration to ischemically damaged hearts despite the observed paucity of cardiomyogenic differentiation of these cells. © 2015 American Heart Association, Inc.

Designing and Implementation of a Heart Failure Telemonitoring System

PubMed Central

Safdari, Reza; Jafarpour, Maryam; Mokhtaran, Mehrshad; Naderi, Nasim

2017-01-01

Introduction: The aim of this study was to identify patients at-risk, enhancing self-care management of HF patients at home and reduce the disease exacerbations and readmissions. Method: In this research according to standard heart failure guidelines and Semi-structured interviews with 10 heart failure Specialists, a draft heart failure rule set for alerts and patient instructions was developed. Eventually, the clinical champion of the project vetted the rule set. Also we designed a transactional system to enhance monitoring and follow up of CHF patients. With this system, CHF patients are required to measure their physiological measurements (vital signs and body weight) every day and to submit their symptoms using the app. additionally, based on their data, they will receive customized notifications and motivation messages to classify risk of disease exacerbation. The architecture of system comprised of six major components: 1) a patient data collection suite including a mobile app and website; 2) Data Receiver; 3) Database; 4) a Specialists expert Panel; 5) Rule engine classifier; 6) Notifier engine. Results: This system has implemented in Iran for the first time and we are currently in the testing phase with 10 patients to evaluate the technical performance of our system. The developed expert system generates alerts and instructions based on the patient’s data and the notify engine notifies responsible nurses and physicians and sometimes patients. Detailed analysis of those results will be reported in a future report. Conclusion: This study is based on the design of a telemonitoring system for heart failure self-care that intents to overcome the gap that occurs when patients discharge from the hospital and tries to accurate requirement of readmission. A rule set for classifying and resulting automated alerts and patient instructions for heart failure telemonitoring was developed. It also facilitates daily communication among patients and heart failure clinicians so any deterioration in health could be identified immediately. PMID:29114106

Designing and Implementation of a Heart Failure Telemonitoring System.

PubMed

Safdari, Reza; Jafarpour, Maryam; Mokhtaran, Mehrshad; Naderi, Nasim

2017-09-01

The aim of this study was to identify patients at-risk, enhancing self-care management of HF patients at home and reduce the disease exacerbations and readmissions. In this research according to standard heart failure guidelines and Semi-structured interviews with 10 heart failure Specialists, a draft heart failure rule set for alerts and patient instructions was developed. Eventually, the clinical champion of the project vetted the rule set. Also we designed a transactional system to enhance monitoring and follow up of CHF patients. With this system, CHF patients are required to measure their physiological measurements (vital signs and body weight) every day and to submit their symptoms using the app. additionally, based on their data, they will receive customized notifications and motivation messages to classify risk of disease exacerbation. The architecture of system comprised of six major components: 1) a patient data collection suite including a mobile app and website; 2) Data Receiver; 3) Database; 4) a Specialists expert Panel; 5) Rule engine classifier; 6) Notifier engine. This system has implemented in Iran for the first time and we are currently in the testing phase with 10 patients to evaluate the technical performance of our system. The developed expert system generates alerts and instructions based on the patient's data and the notify engine notifies responsible nurses and physicians and sometimes patients. Detailed analysis of those results will be reported in a future report. This study is based on the design of a telemonitoring system for heart failure self-care that intents to overcome the gap that occurs when patients discharge from the hospital and tries to accurate requirement of readmission. A rule set for classifying and resulting automated alerts and patient instructions for heart failure telemonitoring was developed. It also facilitates daily communication among patients and heart failure clinicians so any deterioration in health could be identified immediately.

Development of electrocardiogram intervals during growth of FVB/N neonate mice

PubMed Central

2010-01-01

Background Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice. Results We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography. Conclusions We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies. PMID:20735846

Atypical Pupillary Light Reflex and Heart Rate Variability in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Daluwatte, Chathuri; Miles, Judith H.; Christ, Shawn E.; Beversdorf, David Q.; Takahashi, T. Nicole; Yao, Gang

2013-01-01

We investigated pupillary light reflex (PLR) in 152 children with ASD, 116 typically developing (TD) children, and 36 children with non-ASD neurodevelopmental disorders (NDDs). Heart rate variability (HRV) was measured simultaneously to study potential impairments in the autonomic nervous system (ANS) associated with ASD. The results showed that…

A novel protein involved in heart development in Ambystoma mexicanum is localized in endoplasmic reticulum.

PubMed

Jia, P; Zhang, C; Huang, X P; Poda, M; Akbas, F; Lemanski, S L; Erginel-Unaltuna, N; Lemanski, L F

2008-11-01

The discovery of the naturally occurring cardiac non-function (c) animal strain in Ambystoma mexicanum (axolotl) provides a valuable animal model to study cardiomyocyte differentiation. In homozygous mutant animals (c/c), rhythmic contractions of the embryonic heart are absent due to a lack of organized myofibrils. We have previously cloned a partial sequence of a peptide cDNA (N1) from an anterior-endoderm-conditioned-medium RNA library that had been shown to be able to rescue the mutant phenotype. In the current studies we have fully cloned the N1 full length cDNA sequence from the library. N1 protein has been detected in both adult heart and skeletal muscle but not in any other adult tissues. GFP-tagged expression of the N1 protein has revealed localization of the N1 protein in the endoplasmic reticulum (ER). Results from in situ hybridization experiments have confirmed the dramatic decrease of expression of N1 mRNA in mutant (c/c) embryos indicating that the N1 gene is involved in heart development.

Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate.

PubMed

Woerman, Amanda L; Mendelowitz, David

2013-07-01

Sulfur dioxide (SO₂) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO₂ exposure. Pregnant Sprague-Dawley dams and their pups were exposed to 5 parts per million SO₂ for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO₂ exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO₂ exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO₂ exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO₂ exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO₂ exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO₂ exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons. Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO₂-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart.

BMI change during puberty and the risk of heart failure.

PubMed

Kindblom, J M; Bygdell, M; Sondén, A; Célind, J; Rosengren, A; Ohlsson, C

2018-03-12

Hospitalization for heart failure amongst younger men has increased. The reason for this is unknown but it coincides with the obesity epidemic. The aim of this study was to evaluate the association between childhood BMI (Body Mass Index) and BMI change during puberty for risk of adult heart failure in men. Using the BMI Epidemiology Study (BEST), a population-based study in Gothenburg, Sweden, we collected information on childhood BMI at age 8 years and BMI change during puberty (BMI at age 20 - BMI at 8) for men born 1945-1961, followed until December 2013 (n = 37 670). BMI was collected from paediatric growth charts and mandatory military conscription tests. Information on heart failure was retrieved from high-quality national registers (342 first hospitalizations for heart failure). BMI change during puberty was independently of childhood BMI associated with risk of heart failure in a nonlinear J-shaped manner. Subjects in the upper quartile of BMI change during puberty (Q4) had more than twofold increased risk of heart failure compared with subjects in Q1 [HR (Hazard Ratio) = 2.29, 95% CI (Confidence Interval) 1.68-3.12]. Childhood BMI was not independently associated with risk of heart failure. Boys developing overweight during puberty (HR 3.14; 95% CI 2.25-4.38) but not boys with childhood overweight that normalized during puberty (HR 1.12, 95% CI 0.63-2.00) had increased risk of heart failure compared with boys without childhood or young adult overweight. BMI change during puberty is a novel risk factor for adult heart failure in men. © 2018 The Association for the Publication of the Journal of Internal Medicine.

Cardiac Ablation of Rheb1 Induces Impaired Heart Growth, Endoplasmic Reticulum-Associated Apoptosis and Heart Failure in Infant Mice

PubMed Central

Cao, Yunshan; Tao, Lichan; Shen, Shutong; Xiao, Junjie; Wu, Hang; Li, Beibei; Wu, Xiangqi; Luo, Wen; Xiao, Qi; Hu, Xiaoshan; Liu, Hailang; Nie, Junwei; Lu, Shuangshuang; Yuan, Baiyin; Han, Zhonglin; Xiao, Bo; Yang, Zhongzhou; Li, Xinli

2013-01-01

Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure. PMID:24351823

Coronary heart disease is not significantly linked to acute kidney injury identified using Acute Kidney Injury Group criteria.

PubMed

Yayan, Josef

2012-01-01

Patients with unstable angina or myocardial infarction are at risk of acute kidney injury, which may be aggravated by the iodine-containing contrast agent used during coronary angiography; however, the relationship between these two conditions remains unclear. The current study investigated the relationship between acute kidney injury and coronary heart disease prior to coronary angiography. All patients were evaluated after undergoing coronary angiography in the cardiac catheterization laboratory of the Vinzentius Hospital in Landau, Germany, in 2011. The study group included patients with both acute coronary heart disease and acute kidney injury (as defined according to the classification of the Acute Kidney Injury Group); the control group included patients without acute coronary heart disease. Serum creatinine profiles were evaluated in all patients, as were a variety of demographic and health characteristics. Of the 303 patients examined, 201 (66.34%) had coronary artery disease. Of these, 38 (18.91%) also had both acute kidney injury and acute coronary heart disease prior to and after coronary angiography, and of which in turn 34 (16.91%) had both acute kidney injury and acute coronary heart disease only prior to the coronary angiography. However, the occurrence of acute kidney injury was not significantly related to the presence of coronary heart disease (P = 0.95, Chi-square test). The results of this study indicate that acute kidney injury is not linked to acute coronary heart disease. However, physicians should be aware that many coronary heart patients may develop kidney injury while hospitalized for angiography.

Hemodynamics of physiological blood flow in the aorta with nonlinear anisotropic heart valve

NASA Astrophysics Data System (ADS)

Sotiropoulos, Fotis; Gilmanov, Anvar; Stolarski, Henryk

2016-11-01

The hemodynamic blood flow in cardiovascular system is one of the most important factor, which causing several vascular diseases. We developed a new Curvilinear Immersed Boundary - Finite Element - Fluid Structure Interaction (CURVIB-FE-FSI) method to analyze hemodynamic of pulsatile blood flow in a real aorta with nonlinear anisotropic aortic valve at physiological conditions. Hyperelastic material model, which is more realistic for describing heart valve have been incorporated in the CURVIB-FE-FSI code to simulate interaction of aortic heart valve with pulsatile blood flow. Comparative studies of hemodynamics for linear and nonlinear models of heart valve show drastic differences in blood flow patterns and hence differences of stresses causing impact at leaflets and aortic wall. This work is supported by the Lillehei Heart Institute at the University of Minnesota.

Bumps and Ridges: Trabeculation Effects in Embryonic Heart Development

NASA Astrophysics Data System (ADS)

Battista, Nicholas; Lane, Andrea; Miller, Laura

2014-11-01

Trabeculae form in developing zebrafish hearts for Re on the order of 0.1; effects of trabeculae in this flow is not well understood. Dynamic processes, such as vortex formation, are important in the generation of shear at the endothelial surface layer and strains at the epithelial layer, which aid in proper morphology and functionality. In this study, CFD is used to quantify the effects of Re and idealized trabeculae height on the resulting flows.

GDF15 is a heart-derived hormone that regulates body growth.

PubMed

Wang, Ting; Liu, Jian; McDonald, Caitlin; Lupino, Katherine; Zhai, Xiandun; Wilkins, Benjamin J; Hakonarson, Hakon; Pei, Liming

2017-08-01

The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. We show that pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. We demonstrate that blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive (FTT). Together these studies reveal a new endocrine mechanism by which the heart coordinates cardiac function and body growth. Our results also provide a potential mechanism for the well-established clinical observation that children with heart diseases often develop FTT. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Spire, an actin nucleation factor, regulates cell division during Drosophila heart development.

PubMed

Xu, Peng; Johnson, Tamara L; Stoller-Conrad, Jessica R; Schulz, Robert A

2012-01-01

The Drosophila dorsal vessel is a beneficial model system for studying the regulation of early heart development. Spire (Spir), an actin-nucleation factor, regulates actin dynamics in many developmental processes, such as cell shape determination, intracellular transport, and locomotion. Through protein expression pattern analysis, we demonstrate that the absence of spir function affects cell division in Myocyte enhancer factor 2-, Tinman (Tin)-, Even-skipped- and Seven up (Svp)-positive heart cells. In addition, genetic interaction analysis shows that spir functionally interacts with Dorsocross, tin, and pannier to properly specify the cardiac fate. Furthermore, through visualization of double heterozygous embryos, we determines that spir cooperates with CycA for heart cell specification and division. Finally, when comparing the spir mutant phenotype with that of a CycA mutant, the results suggest that most Svp-positive progenitors in spir mutant embryos cannot undergo full cell division at cell cycle 15, and that Tin-positive progenitors are arrested at cell cycle 16 as double-nucleated cells. We conclude that Spir plays a crucial role in controlling dorsal vessel formation and has a function in cell division during heart tube morphogenesis.

Economic cycles and heart disease in Mexico.

PubMed

Quast, Troy; Gonzalez, Fidel

2014-05-01

While a considerable literature has emerged regarding the relationship between the business cycles and mortality rates, relatively little is known regarding how economic fluctuations are related to morbidity. We investigate the relationship between business cycles and heart disease in Mexico using a unique state-level dataset of 512 observations consisting of real GDP and heart disease incidence rates (overall and by age group) from 1995 to 2010. Our study is one of the first to use a state-level panel approach to analyze the relationship between the business cycle and morbidity. Further, the state and year fixed effects employed in our econometric specification reduce possible omitted variable bias. We find a general procyclical, although largely statistically insignificant, contemporaneous relationship. However, an increase in GDP per capita sustained over five years is associated with considerable increases in the incidence rates of ischemic heart disease and hypertension. This procyclical relationship appears strongest in the states with the lowest levels of development and for the oldest age groups. Our results suggest that economic fluctuations may have important lagged effects on heart disease in developing countries. Copyright © 2014 Elsevier Ltd. All rights reserved.

Direct Hydrogel Encapsulation of Pluripotent Stem Cells Enables Ontomimetic Differentiation and Growth of Engineered Human Heart Tissues

PubMed Central

Kerscher, Petra; Turnbull, Irene C; Hodge, Alexander J; Kim, Joonyul; Seliktar, Dror; Easley, Christopher J; Costa, Kevin D; Lipke, Elizabeth A

2016-01-01

Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. Here we demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue. PMID:26826618

Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease.

PubMed

Liu, Shiming; Su, Zhaobing; Tan, Sainan; Ni, Bin; Pan, Hong; Liu, Beihong; Wang, Jing; Xiao, Jianmin; Chen, Qiuhong

2017-08-01

CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.

Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately.

PubMed

Cheng, Wei; Zhou, Ren; Feng, Yan; Wang, Yan

2016-05-16

Epidemiology studies suggest that maternal smoking and passive smoking have strongly resulted in the occurrence of congenital heart defects (CHD) in offspring. Cigarette smoke (CS) can be divided into mainstream smoke (MS) and sidestream smoke (SS); CS chemistry study indicates that significant differences exist in the composition of MS and SS. Therefore, MS and SS were suspected to process toxicity dissimilarly. However, much less was known about the difference in the developmental effects induced by MS and SS. In the current study, heart development was mimicked by mouse embryonic stem cells (ESCs) differentiation. After MS and SS exposure, by tracing the bone morphogenetic protein (BMP)-Smad4 signalling pathway, interruption of downstream gene expression was observed, including Gata4, Mef2c and Nkx2.5, as well as myosin heavy chain and myosin light chain. Specifically, SS caused inhibition of Gata4 expression, even at non-cytotoxic concentration. Further, SS-induced hypoacetylation in promoter regions of Gata4 reflected the orchestration of CS-gene modulation-epigenetic regulation. Even though SS induced apoptosis in ESC-derived cardiomyocytes, the partial clearance in cells with down-regulated Gata4 caused these cells to survive and undergo further differentiation, which laid potential risk for abnormal heart development. These data uncovered the difference between MS and SS on heart development preliminarily. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Reduction of XNkx2-10 expression leads to anterior defects and malformation of the embryonic heart.

PubMed

Allen, Bryan G; Allen-Brady, Kristina; Weeks, Daniel L

2006-10-01

Normal vertebrate heart development depends upon the expression of homeodomain containing proteins related to the Drosophila gene, tinman. In Xenopus laevis, three such genes have been identified in regions that will eventually give rise to the heart, XNkx2-3, XNkx2-5 and XNkx2-10. Although the expression domains of all three overlap in early development, distinctive differences have been noted. By the time the heart tube forms, there is little XNkx2-10 mRNA detected by in situ analysis in the embryonic heart while both XNkx2-3 and XNkx2-5 are clearly present. In addition, unlike XNkx2-3 and XNkx2-5, injection of XNkx2-10 mRNA does not increase the size of the embryonic heart. We have reexamined the expression and potential role of XNkx2-10 in development via oligonucleotide-mediated reduction of XNkx2-10 protein expression. We find that a decrease in XNkx2-10 leads to a broad spectrum of developmental abnormalities including a reduction in heart size. We conclude that XNkx2-10, like XNkx2-3 and XNkx2-5, is necessary for normal Xenopus heart development.

Reduction of XNkx2-10 expression leads to anterior defects and malformation of the embryonic heart

PubMed Central

Allen, Bryan G.; Allen-Brady, Kristina; Weeks, Daniel L.

2007-01-01

Normal vertebrate heart development depends upon the expression of homeodomain containing proteins related to the Drosophila gene, tinman. In Xenopus laevis, three such genes have been identified in regions that will eventually give rise to the heart, XNkx2-3, XNkx2-5 and XNkx2-10. Although the expression domains of all three overlap in early development, distinctive differences have been noted. By the time the heart tube forms, there is little XNkx2-10 mRNA detected by in situ analysis in the embryonic heart while both XNkx2-3 and XNkx2-5 are clearly present. In addition, unlike XNkx2-3 and XNkx2-5, injection of XNkx2-10 mRNA does not increase the size of the embryonic heart. We have reexamined the expression and potential role of XNkx2-10 in development via oligonucleotide-mediated reduction of XNkx2-10 protein expression. We find that a decrease in XNkx2-10 leads to a broad spectrum of developmental abnormalities including a reduction in heart size. We conclude that XNkx2-10, like XNkx2-3 and XNkx2-5, is necessary for normal Xenopus heart development. PMID:16949797

Periods of cardiovascular susceptibility to hypoxia in embryonic american alligators (Alligator mississippiensis)

PubMed Central

Tate, Kevin B.; Rhen, Turk; Eme, John; Kohl, Zachary F.; Crossley, Janna; Elsey, Ruth M.

2016-01-01

During embryonic development, environmental perturbations can affect organisms' developing phenotype, a process known as developmental plasticity. Resulting phenotypic changes can occur during discrete, critical windows of development. Critical windows are periods when developing embryos are most susceptible to these perturbations. We have previously documented that hypoxia reduces embryo size and increases relative heart mass in American alligator, and this study identified critical windows when hypoxia altered morphological, cardiovascular function and cardiac gene expression of alligator embryos. We hypothesized that incubation in hypoxia (10% O2) would increase relative cardiac size due to cardiac enlargement rather than suppression of somatic growth. We exposed alligator embryos to hypoxia during discrete incubation periods to target windows where the embryonic phenotype is altered. Hypoxia affected heart growth between 20 and 40% of embryonic incubation, whereas somatic growth was affected between 70 and 90% of incubation. Arterial pressure was depressed by hypoxic exposure during 50–70% of incubation, whereas heart rate was depressed in embryos exposed to hypoxia during a period spanning 70–90% of incubation. Expression of Vegf and PdgfB was increased in certain hypoxia-exposed embryo treatment groups, and hypoxia toward the end of incubation altered β-adrenergic tone for arterial pressure and heart rate. It is well known that hypoxia exposure can alter embryonic development, and in the present study, we have identified brief, discrete windows that alter the morphology, cardiovascular physiology, and gene expression in embryonic American alligator. PMID:27101296

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.

Development of a questionnaire to measure heart disease risk knowledge in people with diabetes: the Heart Disease Fact Questionnaire.

PubMed

Wagner, Julie; Lacey, Kimberly; Chyun, Deborah; Abbott, Gina

2005-07-01

This paper describes a paper and pencil questionnaire that measures heart disease risk knowledge in people with diabetes. The Heart Disease Fact Questionnaire (HDFQ) is a 25-item questionnaire that was developed to tap into respondents' knowledge of major risk factors for the development of CHD. Approximately half of these items specifically address diabetes-related CHD risk factors. Based on extensive pilot data, the current study analyzed responses from 524 people with diabetes to assess the psychometric properties. The HDFQ is readable to an average 13-year old and imposes little burden. It shows good content and face validity. It demonstrates adequate internal consistency, with Kuder-Richardson-20 formula = 0.77 and good item-total correlations. Item analysis showed a desirable range in P-values. In discriminant function analyses, HDFQ scores differentiated respondents by knowledge of their own cardiovascular health, use of lipid lowering medications, health insurance status, and educational attainment, thus indicating good criterion related validity. This measure of heart disease risk knowledge is brief, understandable to respondents, and easy to administer and score. Its potential for use in research and practice is discussed. Future research should establish norms as well as investigate its test-retest reliability and predictive validity.

Calreticulin Induces Dilated Cardiomyopathy

PubMed Central

Lee, Dukgyu; Oka, Tatsujiro; Hunter, Beth; Robinson, Alison; Papp, Sylvia; Nakamura, Kimitoshi; Srisakuldee, Wattamon; Nickel, Barbara E.; Light, Peter E.; Dyck, Jason R. B.; Lopaschuk, Gary D.; Kardami, Elissavet; Opas, Michal; Michalak, Marek

2013-01-01

Background Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart. Methodology/Principal Findings We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin. Conclusions/Significance We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. PMID:23437120

Health belief model perceptions, knowledge of heart disease, and its risk factors in educated African-American women: an exploration of the relationships of socioeconomic status and age.

PubMed

Jones, Deborah E; Weaver, Michael T; Grimley, Diane; Appel, Susan J; Ard, Jamy

2006-12-01

Heart disease is the leading cause of death for African-American women in the United States. Although African-American women experience higher rates of heart disease with earlier onset and more severe consequences than White women do, they are not aware of their risk for the disease. The Health Belief Model (HBM) has been commonly used to guide preventive interventions in cardiovascular health. However, the HBM has not been evaluated for African-American women regarding its effectiveness. This study explored the perceptions of susceptibility and seriousness of heart disease, and the relationships between socioeconomic status (SES), age, and knowledge of heart disease and its risk factors among 194 educated African-American women from the southern United States. Participants did not perceive themselves to be at high risk for developing heart disease while perceiving heart disease as serious. African-American women who were older perceived heart disease to be more serious than their younger counterparts did. Older women and those with higher SES knew more about heart disease and risk factors. Neither SES nor age moderated the relationship between knowledge and perceived susceptibility or seriousness.

Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies.

PubMed

Braga, J R; Santos, I S O; McDonald, M; Shah, P S; Ross, H J

2012-01-01

Cardiac allograft vasculopathy (CAV) is a significant factor impacting outcomes after heart transplant. We performed a systematic review of risk factors for the development of CAV. A search of electronic databases was performed. The eligibility criteria included cohort and case-control studies with more than 50 adult patients submitted to a heart transplant. The outcome should be CAV diagnosed by angiography and/or intravascular ultrasound (IVUS). Two reviewers performed study selection, data abstraction, and quality assessment. Of 2514 citations, 66 articles were included--46 had 200 participants or less; 61 were single-center; and 44 were retrospective cohorts. The most used definition of CAV using angiography was the detection of any degree of abnormality (21 studies of 58). In studies using IVUS, an intimal thickness ≥0.5 mm was the most used definition (five of eight studies). Quality assessment revealed an inadequate description of patient selection, attrition, and accounting of potential confounders. Donor age, recipient age, recipient gender, etiology of heart failure, ischemic time, human leukocyte antigen matching, cytomegalovirus, lipid profile, and rejection episodes were the most studied factors. Our review indicates that the current evidence is not consistent across different studies. The definite contribution of risk factors for the development of CAV is still to be determined. © 2011 John Wiley & Sons A/S.

Quality of Life for Saudi Patients With Heart Failure: A Cross-Sectional Correlational Study

PubMed Central

AbuRuz, Mohannad Eid; Alaloul, Fawwaz; Saifan, Ahmed; Masa’Deh, Rami; Abusalem, Said

2016-01-01

Introduction: Heart failure is a major public health issue and a growing concern in developing countries, including Saudi Arabia. Most related research was conducted in Western cultures and may have limited applicability for individuals in Saudi Arabia. Thus, this study assesses the quality of life of Saudi patients with heart failure. Materials and Methods: A cross-sectional correlational design was used on a convenient sample of 103 patients with heart failure. Data were collected using the Short Form-36 and the Medical Outcomes Study-Social Support Survey. Results: Overall, the patients’ scores were low for all domains of Quality of Life. The Physical Component Summary and Mental Component Summary mean scores and SDs were (36.7±12.4, 48.8±6.5) respectively, indicating poor Quality of Life. Left ventricular ejection fraction was the strongest predictor of both physical and mental summaries. Conclusion: Identifying factors that impact quality of life for Saudi heart failure patients is important in identifying and meeting their physical and psychosocial needs. PMID:26493415

Comparative effects of sodium channel blockers in short term rat whole embryo culture

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

Nilsson, Mats F, E-mail: Mats.Nilsson@farmbio.uu.se; Sköld, Anna-Carin; Ericson, Ann-Christin

2013-10-15

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the L-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the L-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effectmore » on the heart was studied for a range of concentrations and for a duration up to 3 h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB > bupivacaine > AZA > lidocaine > nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart. - Highlights: • Study of the effect of sodium channel blocking drugs on embryonic heart function • We used a modified method rat whole embryo culture with image analysis. • The drugs tested caused a concentration dependent bradycardia and heart block. • The effect of drugs acting on multiple ion channels is difficult to predict. • This method may be used to detect cardiotoxicity in prenatal development.« less

Heart to Heart Art: Empowering Homeless Children and Youth

ERIC Educational Resources Information Center

Shepard, Jerri; Booth, Deborah

2009-01-01

This article describes Heart to Heart Art, an after-school program developed for homeless children and youth at the YWCA in Spokane, Washington. Pre-service teacher candidates from a local university create meaningful activities that engage homeless students in visual art, music, drama, cooking, and community service. Heart to Heart Art was…

The Framingham Disability Study: relationship of various coronary heart disease manifestations to disability in older persons living in the community.

PubMed Central

Pinsky, J L; Jette, A M; Branch, L G; Kannel, W B; Feinleib, M

1990-01-01

The relation between coronary heart disease and disability was examined in 2,576 community-dwelling women and men ages 55-88 years. These Framingham Study participants were originally recruited in 1948-51 for an examination of cardiovascular disease. Twenty-seven years later, remaining members of the cohort were interviewed to ascertain physical abilities, and a score on a disability scale was assigned. Multivariate logistic analyses examined disability in relation to uncomplicated angina pectoris (AP), complicated AP, and coronary heart disease other than AP, controlling for possible confounders. In younger and older women and men, uncomplicated and complicated AP were associated with disability. Coronary heart disease other than AP was associated with disability only in the younger men. Congestive heart failure predicted disability only in the women. These results suggest that onset of AP should be recognized as a critical point in the development of disability and that AP is a better predictor of disability than is myocardial infarction or coronary insufficiency. PMID:2240306

Cardiogenic Genes Expressed in Cardiac Fibroblasts Contribute to Heart Development and Repair

PubMed Central

Furtado, Milena B.; Costa, Mauro W.; Pranoto, Edward Adi; Salimova, Ekaterina; Pinto, Alex; Lam, Nicholas T.; Park, Anthony; Snider, Paige; Chandran, Anjana; Harvey, Richard P.; Boyd, Richard; Conway, Simon J.; Pearson, James; Kaye, David M.; Rosenthal, Nadia A.

2014-01-01

Rationale Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment but appreciation of their contribution has suffered from incomplete characterization and lack of cell-specific markers. Objective To generate an unbiased comparative gene expression profile of the cardiac fibroblast pool, identify and characterize the role of key genes in cardiac fibroblast function, and determine their contribution to myocardial development and regeneration. Methods and Results High-throughput cell surface and intracellular profiling of cardiac and tail fibroblasts identified canonical MSC and a surprising number of cardiogenic genes, some expressed at higher levels than in whole heart. Whilst genetically marked fibroblasts contributed heterogeneously to interstitial but not cardiomyocyte compartments in infarcted hearts, fibroblast-restricted depletion of one highly expressed cardiogenic marker, Tbx20, caused marked myocardial dysmorphology and perturbations in scar formation upon myocardial infarction. Conclusions The surprising transcriptional identity of cardiac fibroblasts, the adoption of cardiogenic gene programs and direct contribution to cardiac development and repair provokes alternative interpretations for studies on more specialized cardiac progenitors, offering a novel perspective for reinterpreting cardiac regenerative therapies. PMID:24650916

[Nosocomial infections after cardiac surgery in infants and children with congenital heart disease].

PubMed

Barriga, José; Cerda, Jaime; Abarca, Katia; Ferrés, Marcela; Fajuri, Paula; Riquelme, María; Carrillo, Diego; Clavería, Cristián

2014-02-01

Nosocomial infections generate high morbidity and mortality in children undergoing cardiac surgery. To determine risk factors for nosocomial infections in children after congenital heart surgery. A retrospective case-control study, in patients younger than 15 years undergoing surgery for congenital heart disease from January 2007 to December 2011 admitted to the Pediatric Critical Patient Unit (UPC-P) in a university hospital. For cases, the information was analyzed from the first episode of infection. 39 patients who develop infections and 39 controls who did not develop infection were enrolled. The median age of cases was 2 months. We identified a number of factors associated with the occurrence of infections, highlighting in univariate analysis: age, weight, univentricular heart physiology, complexity of the surgical procedure according to RACHS-1 and cardiopulmonary bypass (CPB) time ≥ 200 minutes. Multivariate analysis identified CPB time ≥ 200 minutes as the major risk factor, with an OR of 11.57 (CI: 1.04 to 128.5). CPB time ≥ 200 minutes was the mayor risk factor associated with the development of nosocomial infections.

Evolution and Development of Ventricular Septation in the Amniote Heart

PubMed Central

Poelmann, Robert E.; Groot, Adriana C. Gittenberger-de; Vicente-Steijn, Rebecca; Wisse, Lambertus J.; Bartelings, Margot M.; Everts, Sonja; Hoppenbrouwers, Tamara; Kruithof, Boudewijn P. T.; Jensen, Bjarke; de Bruin, Paul W.; Hirasawa, Tatsuya; Kuratani, Shigeru; Vonk, Freek; van de Put, Jeanne M. M. S.; de Bakker, Merijn A.; Richardson, Michael K.

2014-01-01

During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephants. The vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations. PMID:25192012

Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

PubMed

Shah, Sanjiv J; Aistrup, Gary L; Gupta, Deepak K; O'Toole, Matthew J; Nahhas, Amanda F; Schuster, Daniel; Chirayil, Nimi; Bassi, Nikhil; Ramakrishna, Satvik; Beussink, Lauren; Misener, Sol; Kane, Bonnie; Wang, David; Randolph, Blake; Ito, Aiko; Wu, Megan; Akintilo, Lisa; Mongkolrattanothai, Thitipong; Reddy, Mahendra; Kumar, Manvinder; Arora, Rishi; Ng, Jason; Wasserstrom, J Andrew

2014-01-01

Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

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.

Pericardial constriction after cardiac transplantation.

PubMed

Bansal, Ramesh; Perez, Leandro; Razzouk, Anees; Wang, Nan; Bailey, Leonard

2010-03-01

In this study we present a series of 5 cases that developed constrictive pericarditis after orthotopic heart transplantation. All 5 patients had pericardial effusion of non-infectious etiology in the early post-transplant period. They subsequently presented with heart failure unresponsive to standard medical management. The diagnosis was made by comprehensive echo-Doppler studies. Findings were confirmed at surgical inspection and complete pericardiectomy led to improvement in hemodynamics in 4 patients. One patient had relief from constriction but died of non-cardiac complications. One patient with constriction has been re-listed for transplantation due to intermittent heart block and associated cardiac allograft vasculopathy. Early diagnosis of pericardial constriction after orthotopic heart transplantation requires a high index of clinical suspicion and optimal use of Doppler echocardiography. Early diagnosis and timely surgical pericardiectomy may correct this condition entirely and result in satisfactory long-term results.

Coronary heart disease and risk for cognitive impairment or dementia: Systematic review and meta-analysis.

PubMed

Deckers, Kay; Schievink, Syenna H J; Rodriquez, Maria M F; van Oostenbrugge, Robert J; van Boxtel, Martin P J; Verhey, Frans R J; Köhler, Sebastian

2017-01-01

Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis. We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21-1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0-64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed.

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

PubMed Central

Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Development and Validation of a Heart Atlas to Study Cardiac Exposure to Radiation Following Treatment for Breast Cancer

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

Feng, Mary, E-mail: maryfeng@umich.ed; Moran, Jean M.; Koelling, Todd

2011-01-01

Purpose: Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. Methods and Materials: A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricularmore » branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. Results: The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. Conclusions: This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.« less

[Present status and trend of heart fluid mechanics research based on medical image analysis].

PubMed

Gan, Jianhong; Yin, Lixue; Xie, Shenghua; Li, Wenhua; Lu, Jing; Luo, Anguo

2014-06-01

With introduction of current main methods for heart fluid mechanics researches, we studied the characteristics and weakness for three primary analysis methods based on magnetic resonance imaging, color Doppler ultrasound and grayscale ultrasound image, respectively. It is pointed out that particle image velocity (PIV), speckle tracking and block match have the same nature, and three algorithms all adopt block correlation. The further analysis shows that, with the development of information technology and sensor, the research for cardiac function and fluid mechanics will focus on energy transfer process of heart fluid, characteristics of Chamber wall related to blood fluid and Fluid-structure interaction in the future heart fluid mechanics fields.

[Сhanges in heart rate variability in presymptomatic and symptomatic stages of Parkinson's disease under pharmacological influences: an experimental study].

PubMed

Mamalyga, M L

2013-01-01

The disbalance of autonomic heart regulation (AHR) develops already in the presymptomatic stage of Parkinson's disease. The early symptomatic stage is accompanied by the aggravation of heart dysfunction due to the shift of the autonomic balance towards the increase of sympathetic and decrease of parasympathic effect on the heart. Coronary disorders concomitant to Parkinson's disease increase a risk of life threatening arrhythmia and sudden death syndrome not only in the early symptomatic stage but also in the presymptomatic stage. L-DOPA effectively restores the structure of AHR and prevents the risk of life threatening arrhythmia only in the presymptomatic stage of Parkinson's disease.

[Update on therapy of chronic heart failure. Innovations and studies from last year].

PubMed

Ewen, Sebastian; Linicus, Y; Böhm, M

2015-12-01

Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is crucial. The present review article gives an overview about the innovations in 2014 based on the current guidelines of the European Society of Cardiology. First, improvements in established medication regimens regarding beta blockers and mineralocorticoid receptor antagonists as well as treatment options for heart rate reduction will be explained. Second, new pharmacological developments, such as angiotensin receptor neprilysin inhibition will be discussed. Finally, new insights into common comorbidities of patients with chronic heart failure, such as atrial fibrillation and hyperkalemia will be presented.

Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering.

PubMed

Wu, Shaohua; Duan, Bin; Qin, Xiaohong; Butcher, Jonathan T

2017-03-15

Regeneration and repair of injured or diseased heart valves remains a clinical challenge. Tissue engineering provides a promising treatment approach to facilitate living heart valve repair and regeneration. Three-dimensional (3D) biomimetic scaffolds that possess heterogeneous and anisotropic features that approximate those of native heart valve tissue are beneficial to the successful in vitro development of tissue engineered heart valves (TEHV). Here we report the development and characterization of a novel composite scaffold consisting of nano- and micro-scale fibrous woven fabrics and 3D hydrogels by using textile techniques combined with bioactive hydrogel formation. Embedded nano-micro fibrous scaffolds within hydrogel enhanced mechanical strength and physical structural anisotropy of the composite scaffold (similar to native aortic valve leaflets) and also reduced its compaction. We determined that the composite scaffolds supported the growth of human aortic valve interstitial cells (HAVIC), balanced the remodeling of heart valve ECM against shrinkage, and maintained better physiological fibroblastic phenotype in both normal and diseased HAVIC over single materials. These fabricated composite scaffolds enable the engineering of a living heart valve graft with improved anisotropic structure and tissue biomechanics important for maintaining valve cell phenotypes. Heart valve-related disease is an important clinical problem, with over 300,000 surgical repairs performed annually. Tissue engineering offers a promising strategy for heart valve repair and regeneration. In this study, we developed and tissue engineered living nano-micro fibrous woven fabric/hydrogel composite scaffolds by using textile technique combined with bioactive hydrogel formation. The novelty of our technique is that the composite scaffolds can mimic physical structure anisotropy and the mechanical strength of natural aortic valve leaflet. Moreover, the composite scaffolds prevented the matrix shrinkage, which is major problem that causes the failure of TEHV, and better maintained physiological fibroblastic phenotype in both normal and diseased HAVIC. This work marks the first report of a combination composite scaffold using 3D hydrogel enhanced by nano-micro fibrous woven fabric, and represents a promising tissue engineering strategy to treat heart valve injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Efficient selective screening for heart failure in elderly men and women from the community: A diagnostic individual participant data meta-analysis

PubMed Central

Kievit, Rogier F; Hoes, Arno W; Bots, Michiel L; van Riet, Evelien ES; van Mourik, Yvonne; Bertens, Loes CM; Boonman-de Winter, Leandra JM; den Ruijter, Hester M; Rutten, Frans H

2018-01-01

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64–0.76) to 0.82 (95% CI 0.78–0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70–0.81) to 0.89 (95% CI 0.86–0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure. PMID:29327942

Efficient selective screening for heart failure in elderly men and women from the community: A diagnostic individual participant data meta-analysis.

PubMed

Kievit, Rogier F; Gohar, Aisha; Hoes, Arno W; Bots, Michiel L; van Riet, Evelien Es; van Mourik, Yvonne; Bertens, Loes Cm; Boonman-de Winter, Leandra Jm; den Ruijter, Hester M; Rutten, Frans H

2018-03-01

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64-0.76) to 0.82 (95% CI 0.78-0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70-0.81) to 0.89 (95% CI 0.86-0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.

Management of Sleep Disordered Breathing in Patients with Heart Failure.

PubMed

Oates, Connor P; Ananthram, Manjula; Gottlieb, Stephen S

2018-06-01

This paper reviews treatment options for sleep disordered breathing (SDB) in patients with heart failure. We sought to identify therapies for SDB with the best evidence for long-term use in patients with heart failure and to minimize uncertainties in clinical practice by examining frequently discussed questions: what is the role of continuous positive airway pressure (CPAP) in patients with heart failure? Is adaptive servo-ventilation (ASV) safe in patients with heart failure? To what extent is SDB a modifiable risk factor? Consistent evidence has demonstrated that the development of SDB in patients with heart failure is a poor prognostic indicator and a risk factor for cardiovascular mortality. However, despite numerous available interventions for obstructive sleep apnea and central sleep apnea, it remains unclear what effect these therapies have on patients with heart failure. To date, all major randomized clinical trials have failed to demonstrate a survival benefit with SDB therapy and one major study investigating the use of adaptive servo-ventilation demonstrated harm. Significant questions persist regarding the management of SDB in patients with heart failure. Until appropriately powered trials identify a treatment modality that increases cardiovascular survival in patients with SDB and heart failure, a patient's heart failure management should remain the priority of medical care.

The development of a simulation model of primary prevention strategies for coronary heart disease.

PubMed

Babad, Hannah; Sanderson, Colin; Naidoo, Bhash; White, Ian; Wang, Duolao

2002-11-01

This paper describes the present state of development of a discrete-event micro-simulation model for coronary heart disease prevention. The model is intended to support health policy makers in assessing the impacts on health care resources of different primary prevention strategies. For each person, a set of times to disease events, conditional on the individual's risk factor profile, is sampled from a set of probability distributions that are derived from a new analysis of the Framingham cohort study on coronary heart disease. Methods used to model changes in behavioural and physiological risk factors are discussed and a description of the simulation logic is given. The model incorporates POST (Patient Oriented Simulation Technique) simulation routines.

The Digital Heart Manual: A pilot study of an innovative cardiac rehabilitation programme developed for and with users.

PubMed

Deighan, C; Michalova, L; Pagliari, C; Elliott, J; Taylor, L; Ranaldi, H

2017-08-01

Patients are seeking greater choice and flexibility in how they engage with self-management programmes. While digital innovations offer opportunities to deliver supportive interventions to patients undergoing cardiac rehabilitation little is known about how accessible, useful and acceptable they are for this group. This project developed a digital version of a leading evidenced cardiac rehabilitation programme, the Heart Manual (HM). The prototype was developed and evaluated iteratively in collaboration with end users. Using a mixed methods design 28 participants provided feedback using semi-structured questionnaires and telephone interviews. Rich data revealed the perceived user-friendliness of the HM digital format and its effectiveness at communicating the programme's key messages. It flagged areas requiring development, such as more flexible and intuitive navigation pathways. These suggestions informed the refinement of the resource. This evaluation offers support for the new Digital Heart Manual and confirms the value of employing a user-centred approach when developing and improving online interventions. The system is now in use and recommendations from the evaluation are being translated into quality improvements. The Digital Heart Manual is user friendly and accessible to patients and health professionals, regardless of age, presenting a suitable alternative to the paper version. Copyright © 2017 Elsevier B.V. All rights reserved.

When heart goes “BOOM” to fast. Heart rate greater than 80 as mortality predictor in acute myocardial infarction

PubMed Central

Davidovic, Goran; Iric-Cupic, Violeta; Milanov, Srdjan; Dimitijevic, Aleksandra; Petrovic-Janicijevic, Mirjana

2013-01-01

Many prospective studies established association between high heart rate and increased cardiovascular morbidity and mortality, independently of other risk factors. Heart rate over 80 beats per minute more often leads to atherosclerotic plaque disruption, the main step in developing acute coronary syndrome. Purpose was to investigate the incidence of higher heart rate levels in patients with anterior wall acute myocardial infarction with ST-segment elevation and the influence of heart rate on mortality. Research included 140 patients with anterior wall acute myocardial infarction with ST-segment elevation treated in Coronary Unit, Clinical Center Kragujevac in the period from January 2001-June 2006. Heart rate was calculated as the mean value of baseline and heart rate in the first 30 minutes after admission. Other risk factors were also followed to determine their connection with elevated heart rate. Results showed that the majority of patients survived (over 70%). In a total number of patients, more than 75% had a heart rate levels greater than 80 beats per minute. There was a significant difference in heart rate on addmision between survivors and patients who died, with a greater levels in patients with fatal outcome. Both, univariate and multivariate regression analysis singled out heart rate greater than 80 beats per minute as independent mortality predictor in these patients. Heart rate greater than 80 beats per minute is a major, independent risk factor for morbidity and important predictor of mortality in patients with acute myocardial infarction. PMID:23991346

Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

PubMed

Oliveira, Marcela Silva; Carmona, Fabio; Vicente, Walter V A; Manso, Paulo H; Mata, Karina M; Celes, Mara Rúbia; Campos, Erica C; Ramos, Simone G

2017-04-01

Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β 1 , β 2 -adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β 1 and β 2 receptors and GRK-2, suggesting that this is one of the mechanisms responsible for the exacerbated response of cardiomyocytes to circulating catecholamines. These alterations could explain the irreversible myocardial damage and lipid peroxidation of membranes classically attributed to catecholamine excess, observed in some infants who develop heart failure and postoperative death. Although other factors may be involved, this study confirms that CPB acts as a potent inducer of increased gene expression of β- adrenergic receptors and GRK-2, making the myocardium of these infants more susceptible to the effects of circulating endogenous catecholamines, which may contribute to the development of irreversible myocardial damage and death.

Progress of Heart Rot Following Fire in Bottomland Red Oaks

Treesearch

E. Richard Toole; George M. Furnival

1957-01-01

The most important cause of cull in southern hardwood forests is heart rot that develops from wounds made by fire. This study derived means by which the forester working with bottomland red oaks can determine the amount of decay behind old fire scars and estimate the rot that can be expected from new wounds.

The Heart of the School Counselor: Understanding Passion over the Span of a Career

ERIC Educational Resources Information Center

Sumerlin, Timothy; Littrell, John

2011-01-01

In recent years, school counseling has trended away from some of the vital attributes of the heart, including passion. In this qualitative study, the authors employed a grounded theory and phenomenological approach to understand how school counselors develop and maintain passion over the span of their professional careers. Humbleness and…

Resting heart rate in infants and toddlers: variations associated with early infant diet and the omega 3 fatty acid DHA

USDA-ARS?s Scientific Manuscript database

Although early postnatal nutrition can have long-term effects on developmental processes, the influence of infant diet on the maturation of cardiac development has not been documented. To study this relationship we recorded resting heart-rate (HR) in awake, healthy infants and toddlers exclusively b...

Genome-wide analysis of alternative splicing during human heart development

NASA Astrophysics Data System (ADS)

Wang, He; Chen, Yanmei; Li, Xinzhong; Chen, Guojun; Zhong, Lintao; Chen, Gangbing; Liao, Yulin; Liao, Wangjun; Bin, Jianping

2016-10-01

Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.

scaRNAs regulate splicing and vertebrate heart development.

PubMed

Patil, Prakash; Kibiryeva, Nataliya; Uechi, Tamayo; Marshall, Jennifer; O'Brien, James E; Artman, Michael; Kenmochi, Naoya; Bittel, Douglas C

2015-08-01

Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and splice isoforms of several genes that regulate heart development (e.g., GATA4, NOTCH2, DAAM1, DICER1, MBNL1 and MBNL2). In addition, we used antisense morpholinos to knock down the expression of two scaRNAs (scarna1 and snord94) in zebrafish and saw a corresponding disruption of heart development with an accompanying alteration in splice isoforms of cardiac regulatory genes. Based on these combined results, we hypothesize that scaRNA modification of spliceosomal RNAs assists in fine tuning the spliceosome for dynamic selection of mRNA splice isoforms. Our results are consistent with disruption of splicing patterns during early embryonic development leading to insufficient communication between the first and second heart fields, resulting in conotruncal misalignment and TOF. Our findings represent a new paradigm for determining the mechanisms underlying congenital cardiac malformations. Copyright © 2015. Published by Elsevier B.V.

Heart failure - surgeries and devices

MedlinePlus

... right ventricular assist devices (RVAD) or a total artificial hearts. They are considered for use if you have ... be on a heart-lung bypass machine. Total artificial hearts are being developed, but are not yet in ...

The role of flow in the morphodynamics of embryonic heart

NASA Astrophysics Data System (ADS)

Gharib, Morteza

2017-11-01

Nature has shown us that some hearts do not require valves to achieve unidirectional flow. In its earliest stages, the vertebrate heart consists of a primitive tube that drives blood through a simple vascular network nourishing tissues and other developing organ systems. We have shown that in the case of the embryonic zebrafish heart, an elastic wave resonance mechanism based on impedance mismatches at the boundaries of the heart tube is the likely mechanism responsible for the valveless pumping behavior. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop there is considerable regurgitation, resulting in oscillatory flow between the atrium and ventricle. We show that reversing flows are particularly strong stimuli to endothelial cells and that heart valves form as a developmental response to oscillatory blood flow through the maturing heart.

DNA methylation abnormalities in congenital heart disease.

PubMed

Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

2015-01-01

Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice

PubMed Central

Ye, Maoqing; Coldren, Chris; Liang, Xingqun; Mattina, Teresa; Goldmuntz, Elizabeth; Benson, D. Woodrow; Ivy, Dunbar; Perryman, M.B.; Garrett-Sinha, Lee Ann; Grossfeld, Paul

2010-01-01

Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an ∼7 Mb ‘cardiac critical region’ in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease. PMID:19942620

Using additional information on working hours to predict coronary heart disease: a cohort study

PubMed Central

Kivimäki, Mika; Batty, G. David; Hamer, Mark; Ferrie, Jane E.; Vahtera, Jussi; Virtanen, Marianna; Marmot, Michael G.; Singh-Manoux, Archana; Shipley, Martin J.

2011-01-01

Background Long hours are associated with increased risk of coronary heart disease. Adding information on long hours to traditional risk factors could potentially help improve risk prediction. Objective To examine whether information on long working hours improves the ability of the Framingham risk model to predict coronary heart disease in a low-risk employed population. Design Prospective cohort study; baseline medical examination (1991-1993) and coronary heart disease follow-up to 2004. Settings Civil service departments in London (the Whitehall II study). Participants 7095 adults (2109 women) aged 39 to 62, working full time, and free of coronary heart disease at baseline. Measurements Working hours and the Framingham risk score were measured at baseline. Coronary death and non-fatal myocardial infarction were ascertained from three sources: medical screenings every 5 years, hospital data and register linkage. Results 192 persons had incident coronary heart disease during a median 12.3 year follow-up. After adjustment for the Framingham score, participants working ≥11 hours per day had a 1.67-fold (95% CI: 1.10-2.55) increased risk of coronary heart disease relative to those working 7-8 hours. The addition of working hours to the Framingham score led to a net reclassification improvement of 4.7% (p=0.034), resulting from a better identification of individuals who later developed coronary heart disease (sensitivity gain). Limitations The findings may not be generalizable to populations with a larger proportion of high-risk individuals. Furthermore, the predictive utility of working hours was not validated in an independent cohort. Conclusion Information on working hours may improve prediction of coronary heart disease risk based on the Framingham risk score in low-risk working populations. Primary Funding Source Medical Research Council, British Heart Foundation, BUPA Foundation, UK; National Heart, Lung and Blood Institute and National Institute on Aging, NIH, US. PMID:21464347

Asb2α-Filamin A Axis Is Essential for Actin Cytoskeleton Remodeling During Heart Development.

PubMed

Métais, Arnaud; Lamsoul, Isabelle; Melet, Armelle; Uttenweiler-Joseph, Sandrine; Poincloux, Renaud; Stefanovic, Sonia; Valière, Amélie; Gonzalez de Peredo, Anne; Stella, Alexandre; Burlet-Schiltz, Odile; Zaffran, Stéphane; Lutz, Pierre G; Moog-Lutz, Christel

2018-03-16

Heart development involves differentiation of cardiac progenitors and assembly of the contractile sarcomere apparatus of cardiomyocytes. However, little is known about the mechanisms that regulate actin cytoskeleton remodeling during cardiac cell differentiation. The Asb2α (Ankyrin repeat-containing protein with a suppressor of cytokine signaling box 2) CRL5 (cullin 5 RING E3 ubiquitin ligase) triggers polyubiquitylation and subsequent degradation by the proteasome of FLNs (filamins). Here, we investigate the role of Asb2α in heart development and its mechanisms of action. Using Asb2 knockout embryos, we show that Asb2 is an essential gene, critical to heart morphogenesis and function, although its loss does not interfere with the overall patterning of the embryonic heart tube. We show that the Asb2α E3 ubiquitin ligase controls Flna stability in immature cardiomyocytes. Importantly, Asb2α-mediated degradation of the actin-binding protein Flna marks a previously unrecognized intermediate step in cardiac cell differentiation characterized by cell shape changes and actin cytoskeleton remodeling. We further establish that in the absence of Asb2α, myofibrils are disorganized and that heartbeats are inefficient, leading to embryonic lethality in mice. These findings identify Asb2α as an unsuspected key regulator of cardiac cell differentiation and shed light on the molecular and cellular mechanisms determining the onset of myocardial cell architecture and its link with early cardiac function. Although Flna is known to play roles in cytoskeleton organization and to be required for heart function, this study now reveals that its degradation mediated by Asb2α ensures essential functions in differentiating cardiac progenitors. © 2018 American Heart Association, Inc.

Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system.

PubMed

Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko

2006-01-01

To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease.

Cloning of a newly identified heart-specific troponin I isoform, which lacks the troponin T binding portion, using the yeast hybrid system

PubMed Central

Suzuki, Hideaki; Arakawa, Yasuhiro; Ito, Masaki; Yamada, Hisashi; Horiguchi-Yamada, Junko

2006-01-01

OBJECTIVE To elucidate the molecular pathogenesis behind increased levels of laminin in cardiac muscle cells in cardiomyopathy by using a yeast hybrid screen. The present study reports the cloning of a newly identified heart-specific troponin I isoform, which is putatively linked to laminin. Future studies will explore the functional significance of this connection. METHODS Yeast two-hybrid screen analysis was performed using MLF1-interacting protein (amino acids 1 to 318) as bait. The human heart complementary DNA library was screened by using the yeast-mating method for overnight culture. RESULTS Two final positive clones from the heart library were isolated. These two clones encoded the same protein, a short isoform of human cardiac troponin I (TnI) that lacked TnI exons 5 and 6. The TnI isoform has a heart-specific expression pattern and it shares several sequence features with human cardiac TnI; however, it lacks the troponin T binding portion. CONCLUSION The heart-specific segment of the human cardiac TnI isoform shares several sequence features with human cardiac TnI, but it lacks the troponin T binding portion. These results suggest that the heart-specific TnI isoform may be involved in cardiac development and disease. PMID:18651010

Microstructured Nickel-Titanium Thin Film Leaflets for Hybrid Tissue Engineered Heart Valves Fabricated by Magnetron Sputter Deposition.

PubMed

Loger, K; Engel, A; Haupt, J; Lima de Miranda, R; Lutter, G; Quandt, E

2016-03-01

Heart valves are constantly exposed to high dynamic loading and are prone to degeneration. Therefore, it is a challenge to develop a durable heart valve substitute. A promising approach in heart valve engineering is the development of hybrid scaffolds which are composed of a mechanically strong inorganic mesh enclosed by valvular tissue. In order to engineer an efficient, durable and very thin heart valve for transcatheter implantations, we developed a fabrication process for microstructured heart valve leaflets made from a nickel-titanium (NiTi) thin film shape memory alloy. To examine the capability of microstructured NiTi thin film as a matrix scaffold for tissue engineered hybrid heart valves, leaflets were successfully seeded with smooth muscle cells (SMCs). In vitro pulsatile hydrodynamic testing of the NiTi thin film valve leaflets demonstrated that the SMC layer significantly improved the diastolic sufficiency of the microstructured leaflets, without affecting the systolic efficiency. Compared to an established porcine reference valve model, magnetron sputtered NiTi thin film material demonstrated its suitability for hybrid tissue engineered heart valves.

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.

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

Recent advances in understanding and prevention of sudden cardiac death.

PubMed

Vandenberg, Jamie I; Perry, Matthew D; Hill, Adam P

2017-01-01

There have been tremendous advances in the diagnosis and treatment of heart disease over the last 50 years. Nevertheless, it remains the number one cause of death. About half of heart-related deaths occur suddenly, and in about half of these cases the person was unaware that they had underlying heart disease. Genetic heart disease accounts for only approximately 2% of sudden cardiac deaths, but as it typically occurs in younger people it has been a particular focus of activity in our quest to not only understand the underlying mechanisms of cardiac arrhythmogenesis but also develop better strategies for earlier detection and prevention. In this brief review, we will highlight trends in the recent literature focused on sudden cardiac death in genetic heart diseases and how these studies are contributing to a broader understanding of sudden death in the community.

The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice.

PubMed

Baggio, Laurie L; Ussher, John R; McLean, Brent A; Cao, Xiemin; Kabir, M Golam; Mulvihill, Erin E; Mighiu, Alexandra S; Zhang, Hangjun; Ludwig, Andreas; Seeley, Randy J; Heximer, Scott P; Drucker, Daniel J

2017-11-01

Glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine cells and exerts a broad number of metabolic actions through activation of a single GLP-1 receptor (GLP-1R). The cardiovascular actions of GLP-1 have garnered increasing attention as GLP-1R agonists are used to treat human subjects with diabetes and obesity that may be at increased risk for development of heart disease. Here we studied mechanisms linking GLP-1R activation to control of heart rate (HR) in mice. The actions of GLP-1R agonists were examined on the control of HR in wild type mice (WT) and in mice with cardiomyocyte-selective disruption of the GLP-1R (Glp1r CM-/- ). Complimentary studies examined the effects of GLP-1R agonists in mice co-administered propranolol or atropine. The direct effects of GLP-1R agonism on HR and ventricular developed pressure were examined in isolated perfused mouse hearts ex vivo, and atrial depolarization was quantified in mouse hearts following direct application of liraglutide to perfused atrial preparations ex vivo. Doses of liraglutide and lixisenatide that were equipotent for acute glucose control rapidly increased HR in WT and Glp1r CM-/- mice in vivo. The actions of liraglutide to increase HR were more sustained relative to lixisenatide, and diminished in Glp1r CM-/- mice. The acute chronotropic actions of GLP-1R agonists were attenuated by propranolol but not atropine. Neither native GLP-1 nor lixisenatide increased HR or developed pressure in perfused hearts ex vivo. Moreover, liraglutide had no direct effect on sinoatrial node firing rate in mouse atrial preparations ex vivo. Despite co-localization of HCN4 and GLP-1R in primate hearts, HCN4-directed Cre expression did not attenuate levels of Glp1r mRNA transcripts, but did reduce atrial Gcgr expression in the mouse heart. GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Family caregivers' experiences of caring for patients with heart failure: a descriptive, exploratory qualitative study.

PubMed

Etemadifar, Shahram; Bahrami, Masoud; Shahriari, Mohsen; Farsani, Alireza Khosravi

2015-06-01

Living with heart failure is a complex situation for family caregivers. Many studies addressing the challenges faced by heart failure family caregivers have already been conducted in Western societal settings. Sociocultural factors and perspectives influence the family caring experience and roles. The ethnic/culturally based differences in family caring behavior make this a subject worth further exploration and clarification. This study explores the experiences of family caregivers in Iran of caring for patients with heart failure. A descriptive, exploratory, and qualitative approach was applied to gain authentic insight into the experiences of participants. Purposive sampling was used to recruit 21 family caregivers from three educational hospitals in Isfahan, Iran. Data were collected using semistructured interviews and field notes. Interviews and field notes were transcribed verbatim and concurrently analyzed. Three major themes emerged from the analysis of the transcripts: caregiver uncertainty, lack of familial and organizational support, and Allah-centered caring. Participants believed that they did not have the basic knowledge related to their disease and drugs. In addition, they received little guidance from the healthcare team. Lack of support and insurance as well as financial issues were major problems faced by the caregivers. They accepted the providence of Allah and noted that Allah always helps them accomplish their caregiving responsibilities. The care performed by the caregivers of patients with heart failure exceeds their individual capabilities. Nurses, other healthcare providers, and health policy makers may use the findings of this study to develop more effective programs to address these challenges and to provide more effective support.Sociocultural factors and perspectives were the primary factors affecting the caregiving experiences of participants in this study. Improved understanding of these factors and perspectives will help healthcare providers develop and implement suitable intervention programs for caregivers. Healthcare professionals should develop context-based intervention programs to promote caregiver capabilities and encourage caregivers to participate to facilitate the caregiving roles of caregivers.

Heart failure care in low- and middle-income countries: a systematic review and meta-analysis.

PubMed

Callender, Thomas; Woodward, Mark; Roth, Gregory; Farzadfar, Farshad; Lemarie, Jean-Christophe; Gicquel, Stéphanie; Atherton, John; Rahimzadeh, Shadi; Ghaziani, Mehdi; Shaikh, Maaz; Bennett, Derrick; Patel, Anushka; Lam, Carolyn S P; Sliwa, Karen; Barretto, Antonio; Siswanto, Bambang Budi; Diaz, Alejandro; Herpin, Daniel; Krum, Henry; Eliasz, Thomas; Forbes, Anna; Kiszely, Alastair; Khosla, Rajit; Petrinic, Tatjana; Praveen, Devarsetty; Shrivastava, Roohi; Xin, Du; MacMahon, Stephen; McMurray, John; Rahimi, Kazem

2014-08-01

Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%-64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary.

Heart Failure Care in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

PubMed Central

Callender, Thomas; Woodward, Mark; Roth, Gregory; Farzadfar, Farshad; Lemarie, Jean-Christophe; Gicquel, Stéphanie; Atherton, John; Rahimzadeh, Shadi; Ghaziani, Mehdi; Shaikh, Maaz; Bennett, Derrick; Patel, Anushka; Lam, Carolyn S. P.; Sliwa, Karen; Barretto, Antonio; Siswanto, Bambang Budi; Diaz, Alejandro; Herpin, Daniel; Krum, Henry; Eliasz, Thomas; Forbes, Anna; Kiszely, Alastair; Khosla, Rajit; Petrinic, Tatjana; Praveen, Devarsetty; Shrivastava, Roohi; Xin, Du; MacMahon, Stephen; McMurray, John; Rahimi, Kazem

2014-01-01

Background Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. Methods and Findings Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%–64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. Conclusions The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary PMID:25117081

Estimation of body temperature rhythm based on heart activity parameters in daily life.

PubMed

Sooyoung Sim; Heenam Yoon; Hosuk Ryou; Kwangsuk Park

2014-01-01

Body temperature contains valuable health related information such as circadian rhythm and menstruation cycle. Also, it was discovered from previous studies that body temperature rhythm in daily life is related with sleep disorders and cognitive performances. However, monitoring body temperature with existing devices during daily life is not easy because they are invasive, intrusive, or expensive. Therefore, the technology which can accurately and nonintrusively monitor body temperature is required. In this study, we developed body temperature estimation model based on heart rate and heart rate variability parameters. Although this work was inspired by previous research, we originally identified that the model can be applied to body temperature monitoring in daily life. Also, we could find out that normalized Mean heart rate (nMHR) and frequency domain parameters of heart rate variability showed better performance than other parameters. Although we should validate the model with more number of subjects and consider additional algorithms to decrease the accumulated estimation error, we could verify the usefulness of this approach. Through this study, we expect that we would be able to monitor core body temperature and circadian rhythm from simple heart rate monitor. Then, we can obtain various health related information derived from daily body temperature rhythm.

Causes of sudden death in Addis Ababa, Ethiopia.

PubMed

Schneider, J; Bezabih, K

2001-10-01

The aim of this study was to evaluate the causes of death in individuals who died suddenly in Addis Ababa, Ethiopia. The selection of the cases was based on police reports, which contained a description of sudden unexpected or instantaneous death. The study was performed on necropsies of the Medico legal Department of Menelik II Hospital, in Addis Ababa during the years 1998 and 1999. According to the pathological features of the heart, we classified 92 dead bodies in 3 groups: Group A: Hearts showing adequate morphological changes to explain sudden death (n = 63). Group B: Hearts showing some structural changes, but inadequate to explain sudden death (n = 20). Group C: Normal hearts (n = 7). In two bodies the general autopsy revealed an extra cardiac cause of death. The single most relevant cause of death in group A was coronary artery disease (44 cases) followed by excessive myocardial hypertrophy due to post-rheumatic valvular lesions (7 cases). While the high prevalence of rheumatic heart disease in Ethiopia is well known, the proportion of cases who died due to coronary heart disease is surprising. Though during the last years some African authors assumed that coronary atherosclerosis is on the increase in developing countries the percentage is higher than expected and higher than in other countries where similar studies exist.

Telehealth solutions to enable global collaboration in rheumatic heart disease screening.

PubMed

Lopes, Eduardo Lv; Beaton, Andrea Z; Nascimento, Bruno R; Tompsett, Alison; Dos Santos, Julia Pa; Perlman, Lindsay; Diamantino, Adriana C; Oliveira, Kaciane Kb; Oliveira, Cassio M; Nunes, Maria do Carmo P; Bonisson, Leonardo; Ribeiro, Antônio Lp; Sable, Craig

2018-02-01

Background The global burden of rheumatic heart disease is nearly 33 million people. Telemedicine, using cloud-server technology, provides an ideal solution for sharing images performed by non-physicians with cardiologists who are experts in rheumatic heart disease. Objective We describe our experience in using telemedicine to support a large rheumatic heart disease outreach screening programme in the Brazilian state of Minas Gerais. Methods The Programa de Rastreamento da Valvopatia Reumática (PROVAR) is a prospective cross-sectional study aimed at gathering epidemiological data on the burden of rheumatic heart disease in Minas Gerais and testing of a non-expert, telemedicine-supported model of outreach rheumatic heart disease screening. The primary goal is to enable expert support of remote rheumatic heart disease outreach through cloud-based sharing of echocardiographic images between Minas Gerais and Washington. Secondary goals include (a) developing and sharing online training modules for non-physicians in echocardiography performance and interpretation and (b) utilising a secure web-based system to share clinical and research data. Results PROVAR included 4615 studies that were performed by non-experts at 21 schools and shared via cloud-telemedicine technology. Latent rheumatic heart disease was found in 251 subjects (4.2% of subjects: 3.7% borderline and 0.5% definite disease). Of the studies, 50% were preformed on full functional echocardiography machines and transmitted via Digital Imaging and Communications in Medicine (DICOM) and 50% were performed on handheld echocardiography machines and transferred via a secure Dropbox connection. The average time between study performance date and interpretation was 10 days. There was 100% success in initial image transfer. Less than 1% of studies performed by non-experts could not be interpreted. Discussion A sustainable, low-cost telehealth model, using task-shifting with non-medical personal in low and middle income countries can improve access to echocardiography for rheumatic heart disease.

Evaluation of humoral immunity profiles to identify heart recipients at risk for development of severe infections: A multicenter prospective study.

PubMed

Sarmiento, Elizabeth; Jaramillo, Maria; Calahorra, Leticia; Fernandez-Yañez, Juan; Gomez-Sanchez, Miguel; Crespo-Leiro, Maria G; Paniagua, Maria; Almenar, Luis; Cebrian, Monica; Rabago, Gregorio; Levy, Beltran; Segovia, Javier; Gomez-Bueno, Manuel; Lopez, Javier; Mirabet, Sonia; Navarro, Joaquin; Rodriguez-Molina, Juan Jose; Fernandez-Cruz, Eduardo; Carbone, Javier

2017-05-01

New biomarkers are necessary to improve detection of the risk of infection in heart transplantation. We performed a multicenter study to evaluate humoral immunity profiles that could better enable us to identify heart recipients at risk of severe infections. We prospectively analyzed 170 adult heart recipients at 8 centers in Spain. Study points were before transplantation and 7 and 30 days after transplantation. Immune parameters included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific antibody to pneumococcal polysaccharide antigens (anti-PPS) and to cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical follow-up period lasted 6 months. Clinical outcome was need for intravenous anti-microbials for therapy of infection. During follow-up, 53 patients (31.2%) developed at least 1 severe infection. We confirmed that IgG hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for infection in general, bacterial infections in particular, and CMV disease. At Day 7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was more strongly associated with the outcome (adjusted odds ratio 7.40; 95% confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of anti-CMV antibody titers and lower anti-PPS antibody concentrations were independent predictors of CMV disease and bacterial infections, respectively. Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection. Early immunologic monitoring of humoral immunity profiles proved useful for the identification of heart recipients who are at risk of severe infection. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Technology platform development for targeted plasma metabolites in human heart failure.

PubMed

Chan, Cy X'avia; Khan, Anjum A; Choi, Jh Howard; Ng, Cm Dominic; Cadeiras, Martin; Deng, Mario; Ping, Peipei

2013-01-01

Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic biomarkers for diagnostic and therapeutic development of heart failure patients.

Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure.

PubMed

Kaimoto, Satoshi; Hoshino, Atsushi; Ariyoshi, Makoto; Okawa, Yoshifumi; Tateishi, Shuhei; Ono, Kazunori; Uchihashi, Motoki; Fukai, Kuniyoshi; Iwai-Kanai, Eri; Matoba, Satoaki

2017-02-01

Failing heart loses its metabolic flexibility, relying increasingly on glucose as its preferential substrate and decreasing fatty acid oxidation (FAO). Peroxisome proliferator-activated receptor α (PPAR-α) is a key regulator of this substrate shift. However, its role during heart failure is complex and remains unclear. Recent studies reported that heart failure develops in the heart of myosin heavy chain-PPAR-α transgenic mice in a manner similar to that of diabetic cardiomyopathy, whereas cardiac dysfunction is enhanced in PPAR-α knockout mice in response to chronic pressure overload. We created a pressure-overload heart failure model in mice through transverse aortic constriction (TAC) and activated PPAR-α during heart failure using an inducible transgenic model. After 8 wk of TAC, left ventricular (LV) function had decreased with the reduction of PPAR-α expression in wild-type mice. We examined the effect of PPAR-α induction during heart failure using the Tet-Off system. Eight weeks after the TAC operation, LV construction was preserved significantly by PPAR-α induction with an increase in PPAR-α-targeted genes related to fatty acid metabolism. The increase of expression of fibrosis-related genes was significantly attenuated by PPAR-α induction. Metabolic rates measured by isolated heart perfusions showed a reduction in FAO and glucose oxidation in TAC hearts, but the rate of FAO preserved significantly owing to the induction of PPAR-α. Myocardial high-energy phosphates were significantly preserved by PPAR-α induction. These results suggest that PPAR-α activation during pressure-overloaded heart failure improved myocardial function and energetics. Thus activating PPAR-α and modulation of FAO could be a promising therapeutic strategy for heart failure. NEW & NOTEWORTHY The present study demonstrates the role of PPAR-α activation in the early stage of heart failure using an inducible transgenic mouse model. Induction of PPAR-α preserved heart function, and myocardial energetics. Activating PPAR-α and modulation of fatty acid oxidation could be a promising therapeutic strategy for heart failure. Copyright © 2017 the American Physiological Society.

Perinatal sulfur dioxide exposure alters brainstem parasympathetic control of heart rate

PubMed Central

Woerman, Amanda L.; Mendelowitz, David

2013-01-01

Aims Sulfur dioxide (SO2) is an air pollutant that impedes neonatal development and induces adverse cardiorespiratory health effects, including tachycardia. Here, an animal model was developed that enabled characterization of (i) in vivo alterations in heart rate and (ii) altered activity in brainstem neurons that control heart rate after perinatal SO2 exposure. Methods and results Pregnant Sprague–Dawley dams and their pups were exposed to 5 parts per million SO2 for 1 h daily throughout gestation and 6 days postnatal. Electrocardiograms were recorded from pups at 5 days postnatal to examine changes in basal and diving reflex-evoked changes in heart rate following perinatal SO2 exposure. In vitro studies employed whole-cell patch-clamp electrophysiology to examine changes in neurotransmission to cardiac vagal neurons within the nucleus ambiguus upon SO2 exposure using a preparation that maintains fictive inspiratory activity recorded from the hypoglossal rootlet. Perinatal SO2 exposure increased heart rate and blunted the parasympathetic-mediated diving reflex-evoked changes in heart rate. Neither spontaneous nor inspiratory-related inhibitory GABAergic or glycinergic neurotransmission to cardiac vagal neurons was altered by SO2 exposure. However, excitatory glutamatergic neurotransmission was decreased by 51.2% upon SO2 exposure. This diminished excitatory neurotransmission was tetrodotoxin-sensitive, indicating SO2 exposure impaired the activity of preceding glutamatergic neurons that synapse upon cardiac vagal neurons. Conclusions Diminished glutamatergic, but unaltered inhibitory neurotransmission to cardiac vagal neurons provides a mechanism for the observed SO2-induced elevated heart rate via an impairment of brainstem cardioinhibitory parasympathetic activity to the heart. PMID:23504550

Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy.

PubMed

Cui, Weina; Jang, Albert; Zhang, Pengyuan; Thompson, Brian; Townsend, DeWayne; Metzger, Joseph M; Zhang, Jianyi

2015-01-01

Duchenne muscular dystrophy (DMD) is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS) approach to measure myocardial bioenergetics in the heart in vivo. Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D -Image Selected In vivo Spectroscopy (3D-ISIS) sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59±0.13 vs 2.37±0.25, p<0.05). Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non-invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy.

Nosocomial infections and antibiotic resistance pattern in open-heart surgery patients at Imam Ali Hospital in Kermanshah, Iran.

PubMed

Heydarpour, Fatemeh; Rahmani, Youssef; Heydarpour, Behzad; Asadmobini, Atefeh

2017-01-01

Background: Patients undergoing open heart surgery have a relatively high risk of acquiring nosocomial infections. The development of antibiotic-resistant infections is associated with prolonged hospital stays and mortalities. Objectives: The present study was conducted to investigate nosocomial infections and the antibiotic resistance pattern in bacteria causing these infections in open heart surgery patients at Imam Ali Hospital in Kermanshah in the west of Iran over a 4-year period from March 2011 to March 2014. Materials and methods: The present cross-sectional study was conducted on 135 cases of nosocomial infection among open heart surgery patients. The demographic characteristics and the risk factors of each case of infection were recorded. The antibiotic susceptibility test was carried out using the Minimum Inhibitory Concentration (MIC) method based on the Clinical and Laboratory Standards Institute (CLSI) protocol. The data collected were then analyzed in SPSS-16. Results: Out of the 6,000 patients who underwent open heart surgery during this 4-year period at the selected hospital, nosocomial infections developed in 135 patients (2.25%), 59.3% of whom were female and 40.7% male. Surgery site infection (SSI), pneumonia (PNEU), urinary tract infection (UTI) and blood stream infection (BSI) affected 52.6%, 37%, 9.6% and 0.8% of the cases, respectively. E.coli , Klebsiella spp. and S. aureus were the most common bacteria causing the nosocomial infections. E. coli was most frequently resistant to imipenem (23.3%) Klebsiella spp. to gentamicin (38.5%) S. aureus to co-trimoxazole (54.2%). Conclusion: SSI had a high prevalence in this study. Further studies should therefore be conducted to examine the risk factors associated with SSI in open heart surgery. Various studies have shown that antibiotic resistance patterns are different in different regions. Finding a definitive treatment therefore requires an antibiogram.

Twist1 Transcriptional Targets in the Developing Atrio-Ventricular Canal of the Mouse

PubMed Central

Vrljicak, Pavle; Cullum, Rebecca; Xu, Eric; Chang, Alex C. Y.; Wederell, Elizabeth D.; Bilenky, Mikhail; Jones, Steven J. M.; Marra, Marco A.; Karsan, Aly; Hoodless, Pamela A.

2012-01-01

Malformations of the cardiovascular system are the most common type of birth defect in humans, frequently affecting the formation of valves and septa. During heart valve and septa formation, cells from the atrio-ventricular canal (AVC) and outflow tract (OFT) regions of the heart undergo an epithelial-to-mesenchymal transformation (EMT) and invade the underlying extracellular matrix to give rise to endocardial cushions. Subsequent maturation of newly formed mesenchyme cells leads to thin stress-resistant leaflets. TWIST1 is a basic helix-loop-helix transcription factor expressed in newly formed mesenchyme cells of the AVC and OFT that has been shown to play roles in cell survival, cell proliferation and differentiation. However, the downstream targets of TWIST1 during heart valve formation remain unclear. To identify genes important for heart valve development downstream of TWIST1, we performed global gene expression profiling of AVC, OFT, atria and ventricles of the embryonic day 10.5 mouse heart by tag-sequencing (Tag-seq). Using this resource we identified a novel set of 939 genes, including 123 regulators of transcription, enriched in the valve forming regions of the heart. We compared these genes to a Tag-seq library from the Twist1 null developing valves revealing significant gene expression changes. These changes were consistent with a role of TWIST1 in controlling differentiation of mesenchymal cells following their transformation from endothelium in the mouse. To study the role of TWIST1 at the DNA level we performed chromatin immunoprecipitation and identified novel direct targets of TWIST1 in the developing heart valves. Our findings support a role for TWIST1 in the differentiation of AVC mesenchyme post-EMT in the mouse, and suggest that TWIST1 can exert its function by direct DNA binding to activate valve specific gene expression. PMID:22815831

On Two Hearts and Other Coronary Reflections.

ERIC Educational Resources Information Center

Flannery, Maura C.

1998-01-01

Speculates as to how understanding of heart disease has developed and provides insight into how medical science makes progress. Summarizes the state of knowledge on arteriosclerosis, heart attacks, and exercising the heart. Contains 23 references. (DDR)

Translational Applications of Tissue Engineering in Cardiovascular Medicine.

PubMed

Dogan, Arin; Elcin, A Eser; Elcin, Y Murat

2017-03-26

Cardiovascular diseases are the leading cause of global deaths. The current paradigm in medicine seeks novel approaches for the treatment of progressive or end-stage diseases. The organ transplantation option is limited in availability, and unfortunately, a significant number of patients are lost while waiting for donor organs. Animal studies have shown that upon myocardial infarction, it is possible to stop adverse remodeling in its tracks and reverse with tissue engineering methods. Regaining the myocardium function and avoiding further deterioration towards heart failure can benefit millions of people with a significantly lesser burden on healthcare systems worldwide. The advent of induced pluripotent stem cells brings the unique advantage of testing candidate drug molecules on organ-on-chip systems, which mimics human heart in vitro. Biomimetic three-dimensional constructs that contain disease-specific or normal cardiomyocytes derived from human induced pluripotent stem cells are a useful tool for screening drug molecules and studying dosage, mode of action and cardio-toxicity. Tissue engineering approach aims to develop the treatments for heart valve deficiency, ischemic heart disease and a wide range of vascular diseases. Translational research seeks to improve the patient's quality of life, progressing towards developing cures, rather than treatments. To this end, researchers are working on tissue engineered heart valves, blood vessels, cardiac patches, and injectable biomaterials, hence developing new ways for engineering bio-artificial organs or tissue parts that the body will adopt as its own. In this review, we summarize translational methods for cardiovascular tissue engineering and present useful tables on pre-clinical and clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

4D display of the outflow track of embryonic-chick hearts (HH 14-19) using a high speed streak mode OCT

NASA Astrophysics Data System (ADS)

Ma, Siyu; Wang, Rui; Goodwin, Richard L.; Markwald, Roger R.; Borg, Thomas K.; Runyan, Raymond B.; Gao, Zhi

2013-02-01

Congenital Heart Disease (CHD) is the most common congenital malformation in newborns in the US. Although knowledge of CHD is limited, altered hemodynamic conditions are suspected as the factor that stimulates cardiovascular cell response, resulting in the heart morphology remodeling that ultimately causes CHDs. Therefore, one of recent efforts in CHD study is to develop high-speed imaging tools to correlate the rapidly changing hemodynamic condition and the morphological adaptations of an embryonic heart in vivo. We have developed a high-speed streak mode OCT that works at the center wavelength of 830 nm and is capable of providing images (292x220 μm2) of the outflow tract of an embryonic chick heart at the rate of 1000 Hz. The modality can provide a voxel resolution in the range of 10 μm3, and the spectral resolution allows a depth range of 1.63 mm. In the study reported here, each of the 4D images of an outflow tract was recorded for 2 seconds. The recording was conducted every 2 hours (HH17 to HH18), 3 hours (HH14 to HH17), and 4 hours (HH18 to HH19). Because of the fast scan speed, there is no need for postacquisition processing such as use of gating techniques to provide a fine 3D structure. In addition, more details of the outflow tract are preserved in the recorded images. The 4D images can be used in the future to determine the role of blood flow in CHD development.

hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function.

PubMed

Ye, Junqiang; Beetz, Nadine; O'Keeffe, Sean; Tapia, Juan Carlos; Macpherson, Lindsey; Chen, Weisheng V; Bassel-Duby, Rhonda; Olson, Eric N; Maniatis, Tom

2015-06-09

We report that mice lacking the heterogeneous nuclear ribonucleoprotein U (hnRNP U) in the heart develop lethal dilated cardiomyopathy and display numerous defects in cardiac pre-mRNA splicing. Mutant hearts have disorganized cardiomyocytes, impaired contractility, and abnormal excitation-contraction coupling activities. RNA-seq analyses of Hnrnpu mutant hearts revealed extensive defects in alternative splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d). Loss of hnRNP U expression in cardiomyocytes also leads to aberrant splicing of the pre-mRNA encoding the excitation-contraction coupling component Junctin. We found that the protein product of an alternatively spliced Junctin isoform is N-glycosylated at a specific asparagine site that is required for interactions with specific protein partners. Our findings provide conclusive evidence for the essential role of hnRNP U in heart development and function and in the regulation of alternative splicing.

Analysis of the acoustic spectral signature of prosthetic heart valves in patients experiencing atrial fibrillation

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

Scott, D.D.; Jones, H.E.

1994-05-06

Prosthetic heart valves have increased the life span of many patients with life threatening heart conditions. These valves have proven extremely reliable adding years to what would have been weeks to a patient`s life. Prosthetic valves, like the heart however, can suffer from this constant work load. A small number of valves have experienced structural fractures of the outlet strut due to fatigue. To study this problem a non-intrusive method to classify valves has been developed. By extracting from an acoustic signal the opening sounds which directly contain information from the outlet strut and then developing features which are suppliedmore » to an adaptive classification scheme (neural network) the condition of the valve can be determined. The opening sound extraction process has proved to be a classification problem itself. Due to the uniqueness of each heart and the occasional irregularity of the acoustic pattern it is often questionable as to the integrity of a given signal (beat), especially one occurring during an irregular beat pattern. A common cause of these irregular patterns is a condition known as atrial fibrillation, a prevalent arrhythmia among patients with prosthetic hear valves. Atrial fibrillation is suspected when the ECG shows no obvious P-waves. The atria do not contract and relax correctly to help contribute to ventricular filling during a normal cardiac cycle. Sometimes this leads to irregular patterns in the acoustic data. This study compares normal beat patterns to irregular patterns of the same heart. By analyzing the spectral content of the beats it can be determined whether or not these irregular patterns can contribute to the classification of a heart valve or if they should be avoided. The results have shown that the opening sounds which occur during irregular beat patterns contain the same spectral information as the opening which occur during a normal beat pattern of the same heart and these beats can be used for classification.« less

Participation in Heart-Healthy Behaviors: A Secondary Analysis of the American Heart Association Go Red Heart Match Data.

PubMed

Arslanian-Engoren, Cynthia; Eastwood, Jo-Ann; De Jong, Marla J; Berra, Kathy

2015-01-01

The American Heart Association created Go Red Heart Match, a free and secure online program that enables women to connect with each other to fight heart disease either personally or as a caregiver for someone with heart disease. Through these connections, participants have an opportunity to develop a personal, private, and supportive relationship with other women; share common experiences; and motivate and encourage each other to follow a heart-healthy lifestyle. The aims of this study were to describe the demographic characteristics of the Go Red Heart Match responders and to determine whether participation in the program prompted participants to engage in heart-healthy behaviors. A secondary analysis of data collected as part of a needs assessment survey from the American Heart Association Go Red Heart Match was conducted. A total of 117 (35%) of the 334 invited women completed the survey. Most responders were female, married, and college educated. A total of 105 (90%) responders were diagnosed with a type of heart disease or stroke and 77 (73%) responders had undergone treatment. As a result of participating in the program, 75% of the responders reported the following improvements in heart-healthy behaviors: eating a more heart-healthy diet (54%), exercising more frequently (53%), losing weight (47%), and quitting smoking (10%). Responders who had a diagnosis of heart attack (n = 48) were more likely (P = .003) to quit smoking than were those with other diagnoses (n = 69). Notably, 48% of responders reported encouraging someone else in their life to speak to their doctor about their risk for heart disease. Most women who participated in Heart Match reported engaging in new heart-healthy behaviors. The findings support expanding the existing program in a more diverse population as a potentially important way to reach women and encourage cardiovascular disease risk reduction for those with heart disease and stroke.

The use of HeartQoL in patients with coronary heart disease: Association with risk factors and European reference values. The EUROASPIRE IV study of the European Society of Cardiology.

PubMed

De Smedt, Delphine; Clays, Els; Höfer, Stefan; Oldridge, Neil; Kotseva, Kornelia; Maggioni, Aldo Pietro; Pogosova, Nana; Dolzhenko, Maryna; De Bacquer, Dirk

2016-07-01

HeartQoL is a recently developed core health-related quality of life instrument for patients with coronary heart disease. The current study aims to investigate its association with patients' coronary risk profile and to provide reference values for patients with coronary heart disease across Europe. Analyses are based on the EUROASPIRE IV (EUROpean Action on Secondary and Primary prevention through Intervention to Reduce Events) cross-sectional survey. Patients with a diagnosis of coronary heart disease were examined and interviewed six months to three years after their coronary event. The HeartQoL questionnaire was completed by 7261 coronary heart disease patients. Reference values were calculated and the association with the coronary risk profile was assessed. Significantly worse outcomes were observed in higher-risk patient groups. Both metabolic and behavioural risk factors were associated with worse HeartQoL outcomes. Further, the HeartQoL scores decreased as the number of risk factors increased. The mean global reference values in males were 2.27 ± 0.65 (<60 years), 2.30 ± 0.61 (between 60 and 69 years) and 2.19 ± 0.64 (≥70 years). Likewise, in females, the respective global HeartQoL reference values were 2.02 ± 0.67, 2.01 ± 0.66 and 1.83 ± 0.70. The ceiling effect in males was 11.4%, 10.4% and 7.4% for the three age classes respectively, whereas in females the ceiling effect was 5.2%, 3.5% and 1.9%, respectively. HeartQoL scores were associated with patients' coronary risk profile. The reference values may help other researchers to interpret HeartQoL scores. Further research should focus on the minimal important difference needed to evaluate the effect of therapies and lifestyle changes. © The European Society of Cardiology 2016.

Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

PubMed Central

Ming, Xin; Feng, Yuanming; Liu, Huan; Zhang, Ying; Zhou, Li; Deng, Jun

2015-01-01

Purpose To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years. Methods and Materials A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated. Results The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance. Conclusions Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy. PMID:26630566

Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation.

PubMed

Mekkaoui, Choukri; Huang, Shuning; Chen, Howard H; Dai, Guangping; Reese, Timothy G; Kostis, William J; Thiagalingam, Aravinda; Maurovich-Horvat, Pal; Ruskin, Jeremy N; Hoffmann, Udo; Jackowski, Marcel P; Sosnovik, David E

2012-10-12

The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p < 0.05). This was confirmed histologically by the reduction of HA in the subepicardium from -52.03° ± 2.94° in normal hearts to -37.48° ± 4.05° in the remote zone of the remodeled hearts (p < 0.05). A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Ding, Jingzhong; Hsu, Fang-Chi; Harris, Tamara B; Liu, Yongmei; Kritchevsky, Stephen B; Szklo, Moyses; Ouyang, Pamela; Espeland, Mark A; Lohman, Kurt K; Criqui, Michael H; Allison, Matthew; Bluemke, David A; Carr, J Jeffrey

2009-09-01

Pericardial fat (ie, fat around the heart) may have a direct role in the atherosclerotic process in coronary arteries through local release of inflammation-related cytokines. Cross-sectional studies suggest that pericardial fat is positively associated with coronary artery disease independent of total body fat. We investigated whether pericardial fat predicts future coronary heart disease events. We conducted a case-cohort study in 998 individuals, who were randomly selected from 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants and 147 MESA participants (26 from those 998 individuals) who developed incident coronary heart disease from 2000 to 2005. The volume of pericardial fat was determined from cardiac computed tomography at baseline. The age range of the subjects was 45-84 y (42% men, 45% white, 10% Asian American, 22% African American, and 23% Hispanic). Pericardial fat was positively correlated with both body mass index (correlation coefficient = 0.45, P < 0.0001) and waist circumference (correlation coefficient = 0.57, P < 0.0001). In unadjusted analyses, pericardial fat (relative hazard per 1-SD increment: 1.33; 95% CI: 1.15, 1.54), but not body mass index (1.00; 0.84, 1.18), was associated with the risk of coronary heart disease. Waist circumference (1.14; 0.97, 1.34; P = 0.1) was marginally associated with the risk of coronary heart disease. The relation between pericardial fat and coronary heart disease remained significant after further adjustment for body mass index and other cardiovascular disease risk factors (1.26; 1.01, 1.59). The relation did not differ by sex. Pericardial fat predicts incident coronary heart disease independent of conventional risk factors, including body mass index.

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation

PubMed Central

Bernardo, Bianca C.; Sapra, Geeta; Patterson, Natalie L.; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A.; McMullen, Julie R.

2015-01-01

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions. PMID:26660322

Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

PubMed

Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

2015-01-01

Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

Standard Operating Procedures (SOPs) for Evaluating the Heart in Preclinical Studies of Duchenne Muscular Dystrophy.

PubMed

Duan, Dongsheng; Rafael-Fortney, Jill A; Blain, Alison; Kass, David A; McNally, Elizabeth M; Metzger, Joseph M; Spurney, Christopher F; Kinnett, Kathi

2016-02-01

A recent working group meeting focused on contemporary cardiac issues in Duchenne muscular dystrophy (DMD) was hosted by the National Heart, Lung, and Blood Institute in collaboration with the Parent Project Muscular Dystrophy. An outcome of this meeting was to provide freely available detailed protocols for preclinical animal studies. The goal of these protocols is to improve the quality and reproducibility of cardiac preclinical studies aimed at developing new therapeutics for the prevention and treatment of DMD cardiomyopathy.

Improving Children's Heart Health: A Report from the American Heart Association's Children's Heart Health Conference.

ERIC Educational Resources Information Center

Gidding, Samuel S.; And Others

1995-01-01

This article presents recommendations developed at the 1994 American Heart Association's Children's Heart Health Conference to promote cardiovascular health in children, particularly regarding public health, lifestyle, and behavior. The recommendations cover the areas of physical activity, nutrition, and tobacco, providing suggestions for schools,…

Heart Health Education in the Young

ERIC Educational Resources Information Center

Sunseri, Albert J.; Kruc, Joan E.

1978-01-01

The focus of this article is to examine selected approaches to heart health education, to describe a program the Heart Attack Prevention Program of the Chicago Heart Association is designing and implementing in heart health education, and to make recommendations concerning future development of health education programs by other agencies. (Author)

[Neurological and psychomotor development of foetuses and children with congenital heart disease--causes and prevalence of disorders and long-term prognosis].

PubMed

Herberg, U; Hövels-Gürich, H

2012-06-01

Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population. © Georg Thieme Verlag KG Stuttgart · New York.

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure.

PubMed

Kwekkeboom, Kristine L; Bratzke, Lisa C

2016-01-01

Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life. The 2 authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Thirteen articles describing 9 unique studies met criteria and were included in the review. Five studies tested relaxation strategies, 3 tested meditation strategies, and 1 tested a guided imagery strategy. Of the 9 studies, 7 demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared with attention control or usual care conditions and reduced pain, dyspnea, fatigue, and sleep disturbance within treatment groups (pretreatment to posttreatment). Symptom-related quality of life was improved with meditation compared with attention control and usual care conditions and improved pre- to post-guided imagery. Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings but indicate potential beneficial effects of relaxation, meditation, and guided imagery on heart failure-related symptoms. Future research should test cognitive-behavioral strategies in rigorously designed efficacy trials, using samples selected for their symptom experience, and measure pain, dyspnea, fatigue, and sleep disturbance outcomes with targeted symptom measures.

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure

PubMed Central

Kwekkeboom, Kristine L.; Bratzke, Lisa C.

2015-01-01

Background Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. Objective A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. Methods CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life (QoL). The two authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Results Thirteen articles describing nine unique studies met criteria and were included in the review. Five studies tested relaxation strategies, three tested meditation strategies, and one tested a guided imagery strategy. Seven of the nine studies demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared to attention control or usual care conditions, and reduced pain, dyspnea, fatigue and sleep disturbance within treatment groups (pre- to post-treatment). Symptom-related QoL was improved with meditation compared to attention control and usual care conditions, and improved pre- to post-guided imagery. Conclusions Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings, but indicate potential beneficial effects of relaxation, meditation, and guided imagery on heart failure-related symptoms. Future research should test cognitive-behavioral strategies in rigorously designed efficacy trials, using samples selected for their symptom experience, and measure pain, dyspnea, fatigue, and sleep disturbance outcomes with targeted symptom measures. PMID:26065388

[MR tomography of the heart].

PubMed

Hahn, D; Beer, M; Sandstede, J

2000-10-01

The introduction of magnetic resonance (MR) tomography has fundamentally changed radiological diagnosis for many diseases. Invasive digital subtraction angiography has already been widely replaced by noninvasive MR angiography for most of the vascular diseases. The rapid technical development of MR imaging in recent years has opened new functional imaging techniques. MR imaging of the heart allows simultaneous measurement of morphological and functional parameters in a single noninvasive examination without any radiation exposure. Because of the high spatial resolution and the reproducibility cine MR imaging is now the gold standard for functional analysis. With the improvement of myocardial perfusion and viability studies many diseases of the heart can be diagnosed in a single examination. MR spectroscopy is the only method which allows a view of the metabolism of the heart. New examinations for vascular imaging and flow quantification complete the goal of "one-stop-shop" imaging of the heart. MR imaging is the only diagnostic modality which allows a complete evaluation of many diseases of the heart with one technique, basic examination as well as follow-up studies. The very rapid improvement in MRI will overcome most of the limitations in the near future, especially concerning MR coronary angiography.

Dynamics in prevalence of Down syndrome in children with congenital heart disease.

PubMed

Pfitzer, Constanze; Helm, Paul C; Rosenthal, Lisa-Maria; Berger, Felix; Bauer, Ulrike M M; Schmitt, Katharina Rl

2018-01-01

We assessed the dynamics in the prevalence of children with congenital heart disease (CHD) and Down syndrome in Germany with regard to phenotype, severity, and gender. Data from patients with CHD and Down syndrome born between 1980 and 2014 were analyzed, who are registered with the German National Register for Congenital Heart Defects. One thousand six hundred eighteen CHD patients with Down syndrome were identified. The prevalence of children born with both Down syndrome and CHD was constant from 2005 to 2009 but increased from 2010 to 2014. Regarding CHD groups, complex and simple lesions have become more equal since 2005. The number of simple lesions with shunt has a peak prevalence in the period of 2010-2014. Atrioventricular septal defect was the most common CHD phenotype, but temporal changes were found within the group of CHD phenotypes over the observation period. Our findings suggest a growing number of CHD and Down syndrome, which may be the result of improved medical management and progress in educational, social, and financial support. This development is noteworthy as it adds new aspects to present discussions in the media and political settings. What is known: • Congenital heart disease is regarded to be the most important clinical phenomenon in children with Down syndrome, due to its significant impact on morbidity and mortality. • New developments in prenatal diagnostic and therapy management of congenital heart disease continue to influence the number of patients diagnosed with congenital heart disease and Down syndrome. What is New: • This study provides essential data giving the first overview of the dynamics in the prevalence of congenital heart disease and Down syndrome over an extended length of time up to 2015 in a large patient cohort, taking recent developments into account. • Our data suggest a growing prevalence of congenital heart disease and Down syndrome, which may be the result of improved medical management for Down syndrome patients and progress in educational, social, and financial support for their families; this development is noteworthy as it adds new aspects to the present discussion in the media and political settings.

Hypoxia and fetal heart development.

PubMed

Patterson, A J; Zhang, L

2010-10-01

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

Transient Early Embryonic Expression of Nkx2-5 Mutations Linked to Congenital Heart Defects in Human Causes Heart Defects in Xenopus laevis

PubMed Central

Bartlett, Heather L.; Sutherland, Lillian; Kolker, Sandra J.; Welp, Chelsea; Tajchman, Urszula; Desmarais, Vera; Weeks, Daniel L.

2007-01-01

Nkx2-5 is a homeobox containing transcription factor that is conserved and expressed in organisms that form hearts. Fruit flies lacking the gene (tinman) fail to form a dorsal vessel, mice that are homozygous null for Nkx2-5 form small, deformed hearts, and several human cardiac defects have been linked to dominant mutations in the Nkx2-5 gene. The Xenopus homologs (XNkx2-5) of two truncated forms of Nkx2-5 that have been identified in humans with congenital heart defects were used in the studies reported here. mRNAs encoding these mutations were injected into single cell Xenopus embryos, and heart development was monitored. Our results indicate that the introduction of truncated XNkx2-5 variants leads to three principle developmental defects. The atrial septum and the valve of the atrioventricular canal were both abnormal. In addition, video microscopic timing of heart contraction indicated that embryos injected with either mutant form of XNkx2-5 have conduction defects. PMID:17685485

Presentation of obstructive left heart malformations in infancy.

PubMed Central

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

1994-01-01

This study documents the presentation of acutely life threatening congenital heart disease in infancy in order to assess the performance of screening examinations soon after birth and at 6 weeks of age. All cases of obstructive left heart malformations presenting in infancy in one health region from 1987-91 were analysed retrospectively. Altogether, 120 infants presented with either hypoplastic left heart syndrome, interruption of the aortic arch, coarctation of the aorta, or aortic valve stenosis. Twelve became symptomatic or died within 24 hours. Thirty four had an abnormal neonatal examination, eight of whom were referred. Six more became symptomatic before discharge. Ninety four babies went home, 51 developed heart failure before 6 weeks, and another seven died without diagnosis. Twenty five of 36 (69%) reaching 6 weeks without diagnosis had a second examination which was abnormal in 17. Two babies died undiagnosed after 6 weeks and the other 18 presented at up to 11 months of age. The neonatal and 6 week examinations perform poorly as screening tests for congenital heart disease. A normal neonatal examination does not exclude life threatening congenital heart disease. Images PMID:7820713

Sequential en-face optical coherence tomography imaging and monitoring of Drosophila Melanogaster larval heart

NASA Astrophysics Data System (ADS)

Bradu, A.; Ma, Lisha; Bloor, J.; Podoleanu, A. GH.

2009-02-01

This article demonstrates two modalities to acquire information on cardiac function in larval Drosophila Melanogaster: in-vivo imaging and heartbeat monitoring. To achieve these goals a dedicated imaging instrument able to provide simultaneous en-face Optical Coherence Tomography (OCT) and Laser Scanning Confocal Microscopy (LSCM) images has been developed. With this dual imaging system, the heart can easily be located and visualised within the specimen and the change of the heart shape in a cardiac cycle monitored. The system can easily be switched to a stethoscopic regime, simply by interrupting the scanning of the light beam across the sample, after selecting the point of interest in the imaging regime. Here we have used targeted gene expression to knockdown the myospheroid (mys) gene in the larval heart using a specific RNAi construct. By knocking down a β integrin subunit encoded by mys we have recorded an enlarged heart chamber in both diastolic and systolic states. Also, the fraction of reduction of the chamber diameter was smaller in the knockdown heart. These phenotypic differences indicate that impaired cardiac contractility occurs in the heart where the integrin gene express level is reduced. As far as we are aware, this is for the first time when it is shown in Drosophila that integrins have a direct relationship to a dilated heart defect, and conseqThis article demonstrates two modalities to acquire information on cardiac function in larval Drosophila Melanogaster: in-vivo imaging and heartbeat monitoring. To achieve these goals a dedicated imaging instrument able to provide simultaneous en-face Optical Coherence Tomography (OCT) and Laser Scanning Confocal Microscopy (LSCM) images has been developed. With this dual imaging system, the heart can easily be located and visualised within the specimen and the change of the heart shape in a cardiac cycle monitored. The system can easily be switched to a stethoscopic regime, simply by interrupting the scanning of the light beam across the sample, after selecting the point of interest in the imaging regime. Here we have used targeted gene expression to knockdown the myospheroid (mys) gene in the larval heart using a specific RNAi construct. By knocking down a β integrin subunit encoded by mys we have recorded an enlarged heart chamber in both diastolic and systolic states. Also, the fraction of reduction of the chamber diameter was smaller in the knockdown heart. These phenotypic differences indicate that impaired cardiac contractility occurs in the heart where the integrin gene express level is reduced. As far as we are aware, this is for the first time when it is shown in Drosophila that integrins have a direct relationship to a dilated heart defect, and consequently we demonstrate the utility of Drosophila as model for the study of vertebrate heart disease. By monitoring the heartbeat we also demonstrated a reduction of the heart rate in Tropomyosin mutant compared to the wild type larva.uently we demonstrate the utility of Drosophila as model for the study of vertebrate heart disease. By monitoring the heartbeat we also demonstrated a reduction of the heart rate in Tropomyosin mutant compared to the wild type larva.

Cyanotic congenital heart disease and atherosclerosis.

PubMed

Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

2017-06-01

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

HEART: an automated beat-to-beat cardiovascular analysis package using Matlab.

PubMed

Schroeder, M J Mark J; Perreault, Bill; Ewert, D L Daniel L; Koenig, S C Steven C

2004-07-01

A computer program is described for beat-to-beat analysis of cardiovascular parameters from high-fidelity pressure and flow waveforms. The Hemodynamic Estimation and Analysis Research Tool (HEART) is a post-processing analysis software package developed in Matlab that enables scientists and clinicians to document, load, view, calibrate, and analyze experimental data that have been digitally saved in ascii or binary format. Analysis routines include traditional hemodynamic parameter estimates as well as more sophisticated analyses such as lumped arterial model parameter estimation and vascular impedance frequency spectra. Cardiovascular parameter values of all analyzed beats can be viewed and statistically analyzed. An attractive feature of the HEART program is the ability to analyze data with visual quality assurance throughout the process, thus establishing a framework toward which Good Laboratory Practice (GLP) compliance can be obtained. Additionally, the development of HEART on the Matlab platform provides users with the flexibility to adapt or create study specific analysis files according to their specific needs. Copyright 2003 Elsevier Ltd.

RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure.

PubMed

Gao, Chen; Ren, Shuxun; Lee, Jae-Hyung; Qiu, Jinsong; Chapski, Douglas J; Rau, Christoph D; Zhou, Yu; Abdellatif, Maha; Nakano, Astushi; Vondriska, Thomas M; Xiao, Xinshu; Fu, Xiang-Dong; Chen, Jau-Nian; Wang, Yibin

2016-01-01

RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and identified a muscle-specific isoform of an RNA splicing regulator, RBFox1 (also known as A2BP1), as a prominent regulator of alternative RNA splicing during heart failure. Evaluation of developing murine and zebrafish hearts revealed that RBFox1 is induced during postnatal cardiac maturation. However, we found that RBFox1 is markedly diminished in failing human and mouse hearts. In a mouse model, RBFox1 deficiency in the heart promoted pressure overload-induced heart failure. We determined that RBFox1 is a potent regulator of RNA splicing and is required for a conserved splicing process of transcription factor MEF2 family members that yields different MEF2 isoforms with differential effects on cardiac hypertrophic gene expression. Finally, induction of RBFox1 expression in murine pressure overload models substantially attenuated cardiac hypertrophy and pathological manifestations. Together, this study identifies regulation of RNA splicing by RBFox1 as an important player in transcriptome reprogramming during heart failure that influence pathogenesis of the disease.

RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure

PubMed Central

Gao, Chen; Ren, Shuxun; Lee, Jae-Hyung; Qiu, Jinsong; Chapski, Douglas J.; Rau, Christoph D.; Zhou, Yu; Abdellatif, Maha; Nakano, Astushi; Vondriska, Thomas M.; Xiao, Xinshu; Fu, Xiang-Dong; Chen, Jau-Nian; Wang, Yibin

2015-01-01

RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and identified a muscle-specific isoform of an RNA splicing regulator, RBFox1 (also known as A2BP1), as a prominent regulator of alternative RNA splicing during heart failure. Evaluation of developing murine and zebrafish hearts revealed that RBFox1 is induced during postnatal cardiac maturation. However, we found that RBFox1 is markedly diminished in failing human and mouse hearts. In a mouse model, RBFox1 deficiency in the heart promoted pressure overload–induced heart failure. We determined that RBFox1 is a potent regulator of RNA splicing and is required for a conserved splicing process of transcription factor MEF2 family members that yields different MEF2 isoforms with differential effects on cardiac hypertrophic gene expression. Finally, induction of RBFox1 expression in murine pressure overload models substantially attenuated cardiac hypertrophy and pathological manifestations. Together, this study identifies regulation of RNA splicing by RBFox1 as an important player in transcriptome reprogramming during heart failure that influence pathogenesis of the disease. PMID:26619120

Biomarker Guided Therapy in Chronic Heart Failure

PubMed Central

Bektas, Sema

2015-01-01

This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

Cardiac Embryology and Molecular Mechanisms of Congenital Heart Disease: A Primer for Anesthesiologists.

PubMed

Kloesel, Benjamin; DiNardo, James A; Body, Simon C

2016-09-01

Congenital heart disease is diagnosed in 0.4% to 5% of live births and presents unique challenges to the pediatric anesthesiologist. Furthermore, advances in surgical management have led to improved survival of those patients, and many adult anesthesiologists now frequently take care of adolescents and adults who have previously undergone surgery to correct or palliate congenital heart lesions. Knowledge of abnormal heart development on the molecular and genetic level extends and improves the anesthesiologist's understanding of congenital heart disease. In this article, we aim to review current knowledge pertaining to genetic alterations and their cellular effects that are involved in the formation of congenital heart defects. Given that congenital heart disease can currently only occasionally be traced to a single genetic mutation, we highlight some of the difficulties that researchers face when trying to identify specific steps in the pathogenetic development of heart lesions.

Essential but partially redundant roles for POU4F1/Brn-3a and POU4F2/Brn-3b transcription factors in the developing heart

PubMed Central

Maskell, Lauren J; Qamar, Kashif; Babakr, Aram A; Hawkins, Thomas A; Heads, Richard J; Budhram-Mahadeo, Vishwanie S

2017-01-01

Congenital heart defects contribute to embryonic or neonatal lethality but due to the complexity of cardiac development, the molecular changes associated with such defects are not fully understood. Here, we report that transcription factors (TFs) Brn-3a (POU4F1) and Brn-3b (POU4F2) are important for normal cardiac development. Brn-3a directly represses Brn-3b promoter in cardiomyocytes and consequently Brn-3a knockout (KO) mutant hearts express increased Brn-3b mRNA during mid-gestation, which is linked to hyperplastic growth associated with elevated cyclin D1, a known Brn-3b target gene. However, during late gestation, Brn-3b can cooperate with p53 to enhance transcription of pro-apoptotic genes e.g. Bax, thereby increasing apoptosis and contribute to morphological defects such as non-compaction, ventricular wall/septal thinning and increased crypts/fissures, which may cause lethality of Brn-3a KO mutants soon after birth. Despite this, early embryonic lethality in e9.5 double KO (Brn-3a−/− : Brn-3b−/−) mutants indicate essential functions with partial redundancy during early embryogenesis. High conservation between mammals and zebrafish (ZF) Brn-3b (87%) or Brn-3a (76%) facilitated use of ZF embryos to study potential roles in developing heart. Double morphant embryos targeted with morpholino oligonucleotides to both TFs develop significant cardiac defects (looping abnormalities and valve defects) suggesting essential roles for Brn-3a and Brn-3b in developing hearts. PMID:28594399

Alteration of development and gene expression induced by in ovo-nanoinjection of 3-hydroxybenzo[c]phenanthrene into Japanese medaka (Oryzias latipes) embryos.

PubMed

Chen, Kun; Tsutsumi, Yuki; Yoshitake, Shuhei; Qiu, Xuchun; Xu, Hai; Hashiguchi, Yasuyuki; Honda, Masato; Tashiro, Kosuke; Nakayama, Kei; Hano, Takeshi; Suzuki, Nobuo; Hayakawa, Kazuichi; Shimasaki, Yohei; Oshima, Yuji

2017-01-01

Benzo[c]phenanthrene (BcP) is a highly toxic polycyclic aromatic hydrocarbon (PAHs) found throughout the environment. In fish, it is metabolized to 3-hydroxybenzo[c]phenanthrene (3-OHBcP). In the present study, we observed the effects of 1nM 3-OHBcP on the development and gene expression of Japanese medaka (Oryzias latipes) embryos. Embryos were nanoinjected with the chemical after fertilization. Survival, developmental stage, and heart rate of the embryos were observed, and gene expression differences were quantified by messenger RNA sequencing (mRNA-Seq). The exposure to 1nM 3-OHBcP accelerated the development of medaka embryos on the 1st, 4th, and 6th days post fertilization (dpf), and increased heart rates significantly on the 5th dpf. Physical development differences of exposed medaka embryos were consistent with the gene expression profiles of the mRNA-Seq results for the 3rd dpf, which show that the expression of 780 genes differed significantly between the solvent control and 1nM 3-OHBcP exposure groups. The obvious expression changes in the exposure group were found for genes involved in organ formation (eye, muscle, heart), energy supply (ATPase and ATP synthase), and stress-response (heat shock protein genes). The acceleration of development and increased heart rate, which were consistent with the changes in mRNA expression, suggested that 3-OHBcP affects the development of medaka embryos. The observation on the developmental stages and heart beat, in ovo-nanoinjection and mRNA-Seq may be efficient tools to evaluate the effects of chemicals on embryos. Copyright © 2016 Elsevier B.V. All rights reserved.

Hippo signaling impedes adult heart regeneration

PubMed Central

Heallen, Todd; Morikawa, Yuka; Leach, John; Tao, Ge; Willerson, James T.; Johnson, Randy L.; Martin, James F.

2013-01-01

Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control pathway, is a kinase cascade that inhibits developing cardiomyocyte proliferation but it has not been studied postnatally or in fully mature adult cardiomyocytes. Here, we investigated Hippo signaling in adult cardiomyocyte renewal and regeneration. We found that unstressed Hippo-deficient adult mouse cardiomyocytes re-enter the cell cycle and undergo cytokinesis. Moreover, Hippo deficiency enhances cardiomyocyte regeneration with functional recovery after adult myocardial infarction as well as after postnatal day eight (P8) cardiac apex resection and P8 myocardial infarction. In damaged hearts, Hippo mutant cardiomyocytes also have elevated proliferation. Our findings reveal that Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration. Targeting the Hippo pathway in human disease might be beneficial for the treatment of heart disease. PMID:24255096

Impact of Telemedicine in the Screening for Congenital Heart Disease in a Center from Northeast Brazil.

PubMed

de Araújo, Juliana Sousa Soares; Regis, Cláudio Teixeira; Gomes, Renata Grigório Silva; Mourato, Felipe Alves; Mattos, Sandra da Silva

2016-12-01

To describe the incidence of congenital heart disease before and after the establishment of a telemedicine screening program, in a reference center from Northeast Brazil. This is a descriptive, retrospective and comparative study based on the institutional data from a reference center in perinatology for a period of 16 years. Institutional data were collected from a 16-year period (2001-15). Data were divided into two periods: prior to (2001-11) and after (2012-15) the establishment of a telemedicine screening program. After the implementation of the screening process, almost all kinds of heart disease showed a significant increase in their incidence (p  <  0.05). With this, the incidence of major heart diseases approached those specified in developed regions. The implementation of a screening process model for congenital heart diseases can change the context of patients with congenital heart diseases in poor regions. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Resting heart rate and the development of antisocial behavior from age 9 to 14: genetic and environmental influences.

PubMed

Baker, Laura A; Tuvblad, Catherine; Reynolds, Chandra; Zheng, Mo; Lozano, Dora Isabel; Raine, Adrian

2009-01-01

The genetic and environmental basis of a well-replicated association between antisocial behavior (ASB) and resting heart rate was investigated in a longitudinal twin study, based on two measurements between the ages of 9 and 14 years. ASB was defined as a broad continuum of externalizing behavior problems, assessed at each occasion through a composite measure based on parent ratings of trait aggression, delinquent behaviors, and psychopathic traits in their children. Parent ratings of ASB significantly decreased across age from childhood to early adolescence, although latent growth models indicated significant variation and twin similarity in the growth patterns, which were explained almost entirely by genetic influences. Resting heart rate at age 9-10 years old was inversely related to levels of ASB but not change patterns of ASB across age or occasions. Biometrical analyses indicated significant genetic influences on heart rate during childhood, as well as ASB throughout development from age 9 to 14. Both level and slope variation were significantly influenced by genetic factors. Of importance, the low resting heart rate and ASB association was significantly and entirely explained by their genetic covariation, although the heritable component of heart rate explained only a small portion (1-4%) of the substantial genetic variance in ASB. Although the effect size is small, children with low resting heart rate appear to be genetically predisposed toward externalizing behavior problems as early as age 9 years old.

Heart sounds analysis via esophageal stethoscope system in beagles.

PubMed

Park, Sang Hi; Shin, Young Duck; Bae, Jin Ho; Kwon, Eun Jung; Lee, Tae-Soo; Shin, Ji-Yun; Kim, Yeong-Cheol; Min, Gyeong-Deuk; Kim, Myoung hwan

2013-10-01

Esophageal stethoscope is less invasive and easy to handling. And it gives a lot of information. The purpose of this study is to investigate the correlation of blood pressure and heart sound as measured by esophageal stethoscope. Four male beagles weighing 10 to 12 kg were selected as experimental subjects. After general anesthesia, the esophageal stethoscope was inserted. After connecting the microphone, the heart sounds were visualized and recorded through a self-developed equipment and program. The amplitudes of S1 and S2 were monitored real-time to examine changes as the blood pressure increased and decreased. The relationship between the ratios of S1 to S2 (S1/S2) and changes in blood pressure due to ephedrine was evaluated. The same experiment was performed with different concentration of isoflurane. From S1 and S2 in the inotropics experiment, a high correlation appeared with change in blood pressure in S1. The relationship between S1/S2 and change in blood pressure showed a positive correlation in each experimental subject. In the volatile anesthetics experiment, the heart sounds decreased as MAC increased. Heart sounds were analyzed successfully with the esophageal stethoscope through the self-developed program and equipment. A proportional change in heart sounds was confirmed when blood pressure was changed using inotropics or volatile anesthetics. The esophageal stethoscope can achieve the closest proximity to the heart to hear sounds in a non-invasive manner.

Embryonic Heart Progenitors and Cardiogenesis

PubMed Central

Brade, Thomas; Pane, Luna S.; Moretti, Alessandra; Chien, Kenneth R.; Laugwitz, Karl-Ludwig

2013-01-01

The mammalian heart is a highly specialized organ, comprised of many different cell types arising from distinct embryonic progenitor populations during cardiogenesis. Three precursor populations have been identified to contribute to different myocytic and nonmyocytic cell lineages of the heart: cardiogenic mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells (CNCCs). This review will focus on molecular cues necessary for proper induction, expansion, and lineage-specific differentiation of these progenitor populations during cardiac development in vivo. Moreover, we will briefly discuss how the knowledge gained on embryonic heart progenitor biology can be used to develop novel therapeutic strategies for the management of congenital heart disease as well as for improvement of cardiac function in ischemic heart disease. PMID:24086063

Heart failure gene therapy: closer to reality. Professor Walter Koch speaks to Christine Forder, commissioning editor.

PubMed

Koch, Walter J

2009-03-01

Professor Walter Koch is currently a Director at the Center for Translational Medicine and Vice Chairman for Research in the Department of Medicine at Jefferson Medical College, Thomas Jefferson University, PA, USA. Professor Koch started his career as a Research Associate at the Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA. His work is based around heart failure and the molecular mechanisms involved in the regulation of signaling through cardiovascular adrenergic receptors, the study of G-proteincoupled receptor function and signaling, and heart failure gene therapy. His current studies are investigating into the use of novel viral-mediated myocardial gene delivery for use in congestive heart failure, with an aim at developing reproducible surgical means of gene therapy. He is also involved in research to understand novel molecular signaling mechanisms responsible for reversible cardiac injury and potential repair.

Patient Characteristics Predicting Readmission Among Individuals Hospitalized for Heart Failure.

PubMed

O'Connor, Melissa; Murtaugh, Christopher M; Shah, Shivani; Barrón-Vaya, Yolanda; Bowles, Kathryn H; Peng, Timothy R; Zhu, Carolyn W; Feldman, Penny H

2016-02-01

Heart failure is difficult to manage and increasingly common with many individuals experiencing frequent hospitalizations. Little is known about patient factors consistently associated with hospital readmission. A literature review was conducted to identify heart failure patient characteristics, measured before discharge, that contribute to variation in hospital readmission rates. Database searches yielded 950 potential articles, of which 34 studies met inclusion criteria. Patient characteristics generally have a very modest effect on all-cause or heart failure-related readmission within 7 to 180 days of index hospital discharge. A range of cardiac diseases and other comorbidities only minimally increase readmission rates. No single patient characteristic stands out as a key contributor across multiple studies underscoring the challenge of developing successful interventions to reduce readmissions. Interventions may need to be general in design with the specific intervention depending on each patient's unique clinical profile. © The Author(s) 2015.

Patient Characteristics Predicting Readmission Among Individuals Hospitalized for Heart Failure

PubMed Central

O'Connor, Melissa; Murtaugh, Christopher M.; Shah, Shivani; Barrón-Vaya, Yolanda; Bowles, Kathryn H.; Peng, Timothy R.; Zhu, Carolyn W.; Feldman, Penny H.

2015-01-01

Heart failure is difficult to manage and increasingly common with many individuals experiencing frequent hospitalizations. Little is known about patient factors consistently associated with hospital readmission. A literature review was conducted to identify heart failure patient characteristics, measured before discharge, that contribute to variation in hospital readmission rates. Database searches yielded 950 potential articles, of which 34 studies met inclusion criteria. Patient characteristics generally have a very modest effect on all-cause or heart failure–related readmission within 7 to 180 days of index hospital discharge. A range of cardiac diseases and other comorbidities only minimally increase readmission rates. No single patient characteristic stands out as a key contributor across multiple studies underscoring the challenge of developing successful interventions to reduce readmissions. Interventions may need to be general in design with the specific intervention depending on each patient's unique clinical profile. PMID:26180045

Heart Rate and Blood Pressure Variability under Moon, Mars and Zero Gravity Conditions During Parabolic Flights

NASA Astrophysics Data System (ADS)

Aerts, Wouter; Joosen, Pieter; Widjaja, Devy; Varon, Carolina; Vandeput, Steven; Van Huffel, Sabine; Aubert, Andre E.

2013-02-01

Gravity changes during partial-G parabolic flights (0g -0.16g - 0.38g) lead to changes in modulation of the autonomic nervous system (ANS), studied via the heart rate variability (HRV) and blood pressure variability (BPV). HRV and BPV were assessed via classical time and frequency domain measures. Mean systolic and diastolic blood pressure show both increasing trends towards higher gravity levels. The parasympathetic and sympathetic modulation show both an increasing trend with decreasing gravity, although the modulation is sympathetic predominant during reduced gravity. For the mean heart rate, a non-monotonic relation was found, which can be explained by the increased influence of stress on the heart rate. This study shows that there is a relation between changes in gravity and modulations in the ANS. With this in mind, countermeasures can be developed to reduce postflight orthostatic intolerance.

Strain and Torsion Quantification in Mouse Hearts under Dobutamine Stimulation using 2D Multi-Phase MR DENSE

PubMed Central

Zhong, Jia; Yu, Xin

2010-01-01

In the current study, a 2D multi-phase MR displacement encoding with stimulated echoes (DENSE) imaging and analysis method was developed for direct quantification of Lagrangian strain in the mouse heart. Using the proposed method, less than 10 ms temporal resolution and 0.56 mm in-plane resolution were achieved. A validation study that compared strain calculation by DENSE and by MR tagging showed high correlation between the two methods (R2 > 0.80). Regional ventricular wall strain and twist were characterized in mouse hearts at baseline and under dobutamine stimulation. Dobutamine stimulation induced significant increase in radial and circumferential strains and torsion at peak-systole. A rapid untwisting was also observed during early diastole. This work demonstrates the capability of characterizing cardiac functional response to dobutamine stimulation in the mouse heart using 2D multi-phase MR DENSE. PMID:20740659

A Single Center Study of 1,179 Heart Transplant Patients-Factors Affecting Pacemaker Implantation.

PubMed

Wellmann, Petra; Herrmann, Florian Ernst Martin; Hagl, Christian; Juchem, Gerd

2017-03-01

After around 10% of heart transplant patients require pacemaker implantation. The bradyarrhythmias causing pacemaker requirement include sinus node dysfunction (SND) and atrioventricular block (AVB). This study sought to define clinical predictors for pacemaker requirement as well as identify differences in the patient groups developing SND and AVB. Our operative database was used to collect retrospective recipient, donor, and operative data of all patients receiving orthotopic heart transplants between 1981 and 2016. In the 35-year period 1,179 transplants were performed (mean recipient age 45.5 ± 0.5 years, 20.4% female, 90.6% biatrial technique) with bradyarrhythmias requiring pacemaker implantation developing in 135 patients (11.5%). Independent risk factors were prolonged operative time 340 minutes versus 313 minutes (P = 0.027) and a biatrial anastomosis (P = 0.036). Ischemia time, cardiopulmonary bypass time, aortic cross clamp time, and reperfusion time all had no significant effect on pacemaker implantation rates. Similarly, whether the transplant was a reoperation, a retransplant, or performed after primary assist implantation had no effects on pacemaker implantation rates. There was no survival difference between the paced and nonpaced groups. The donor age was higher in the patients who developed AVB as the indication for pacemaker implantation (43 vs 34 years, P = 0.031). Patients with AVB had longer aortic cross clamp times and developed the arrhythmia later than those who developed SND. Use of the bicaval instead of the biatrial technique and shortened operative times should reduce pacemaker requirement after heart transplantation. Survival is not affected by this complication. © 2017 Wiley Periodicals, Inc.

Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development

PubMed Central

Ribas, João; Sadeghi, Hossein; Manbachi, Amir; Leijten, Jeroen; Brinegar, Katelyn; Zhang, Yu Shrike; Ferreira, Lino

2016-01-01

Abstract Cardiovascular diseases are prevalent worldwide and are the most frequent causes of death in the United States. Although spending in drug discovery/development has increased, the amount of drug approvals has seen a progressive decline. Particularly, adverse side effects to the heart and general vasculature have become common causes for preclinical project closures, and preclinical models do not fully recapitulate human in vivo dynamics. Recently, organs-on-a-chip technologies have been proposed to mimic the dynamic conditions of the cardiovascular system—in particular, heart and general vasculature. These systems pay particular attention to mimicking structural organization, shear stress, transmural pressure, mechanical stretching, and electrical stimulation. Heart- and vasculature-on-a-chip platforms have been successfully generated to study a variety of physiological phenomena, model diseases, and probe the effects of drugs. Here, we review and discuss recent breakthroughs in the development of cardiovascular organs-on-a-chip platforms, and their current and future applications in the area of drug discovery and development. PMID:28971113

A Heart Rate Analysis of Developmental Change in Feedback Processing and Rule Shifting from Childhood to Early Adulthood

ERIC Educational Resources Information Center

Crone, Eveline A.; Somsen, Riek J. M.; Zanolie, Kiki; Van der Molen, Maurits W.

2006-01-01

Over the course of development, the ability to switch between different tasks on the basis of feedback cues increases profoundly, but the role of performance monitoring remains unclear. Heart rate indexes can provide critical information about how individuals monitor feedback cues indicating that performance should be adjusted. In this study,…

Heart Rate and VO[subscript 2] Responses to Cycle Ergometry in White and African American Men

ERIC Educational Resources Information Center

Vehrs, Pat R.; Fellingham, Gilbert W.

2006-01-01

The validity of estimates of peak oxygen consumption (VO[subscript 2]peak) using submaximal exercise tests may be compromised when the participants being tested are not similar to the participants used to develop the test. This study compared ethnic differences in the heart rate (HR) and oxygen consumption (VO[subscript 2]) responses to submaximal…

[Pathogenetic and Prognostic Role of Growth Factors in the Development of Chronic Heart Failure].

PubMed

Teplyakov, A T; Berezikova, E N; Shilov, S N; Efremova, A V; Pustovetova, M G; Popova, A A; Grakova, E V; Torim, Y Y; Safronov, I D; Andriyanova, A V

2017-10-01

To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD). We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay. VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient's sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF. A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

Development and Evaluation of Heartbeat: A Machine Perfusion Heart Preservation System.

PubMed

Li, Yongnan; Zeng, Qingdong; Liu, Gang; Du, Junzhe; Gao, Bingren; Wang, Wei; Zheng, Zhe; Hu, Shengshou; Ji, Bingyang

2017-11-01

Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group. The ultrastructure of myocardium suggests better myocardial protection in the Heartbeat group compared with HTK or Celsior-preserved hearts. The myocardial and coronary artery structural and functional integrity was evaluated by immunofluorescence and Western blots in the Heartbeat. In the Heartbeat group, donor hearts maintained a high adenosine triphosphate level. Bcl-2 and Beclin-1 protein demonstrates high expression in the Celsior group. The Heartbeat system can be used to preserve donor hearts, and it could guarantee the myocardial and endothelial function of hearts during machine perfusion. Translating Heartbeat into clinical practice, it is such as to impact on donor heart preservation for cardiac transplantation. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

PubMed

Gepstein, Lior; Kehat, Izhak

2005-02-01

Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

Progress in the development of a transcutaneously powered axial flow blood pump ventricular assist system.

PubMed

Parnis, S M; Conger, J L; Fuqua, J M; Jarvik, R K; Inman, R W; Tamez, D; Macris, M P; Moore, S; Jacobs, G; Sweeney, M J; Frazier, O H

1997-01-01

Development of the Jarvik 2000 intraventricular assist system for long-term support is ongoing. The system integrates the Jarvik 2000 axial flow blood pump with a microprocessor based automatic motor controller to provide response to physiologic demands. Nine devices have been evaluated in vivo (six completed, three ongoing) with durations in excess of 26 weeks. Instrumented experiments include implanted transit-time ultrasonic flow probes and dual micromanometer LV/AoP catheters. Treadmill exercise and heart pacing studies are performed to evaluate control system response to increased heart rates. Pharmacologically induced cardiac dysfunction studies are performed in awake and anesthetized calves to demonstrate control response to simulated heart failure conditions. No deleterious effects or events were encountered during any physiologic studies. No hematologic, renal, hepatic, or pulmonary complications have been encountered in any study. Plasma free hemoglobin levels of 7.0 +/- 5.1 mg/dl demonstrate no device related hemolysis throughout the duration of all studies. Pathologic analysis at explant showed no evidence of thromboembolic events. All pump surfaces were free of thrombus except for a minimal ring of fibrin, (approximately 1 mm) on the inflow bearing. Future developments for permanent implantation will include implanted physiologic control systems, implanted batteries, and transcutaneous energy and data transmission systems.

Cardiorenal syndrome: new developments in the understanding and pharmacologic management.

PubMed

House, Andrew A

2013-10-01

Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.

The use of dornase alpha for post-operative pulmonary atelectasis after congenital heart surgery.

PubMed

Ozturk, Erkut; Tanidir, Ibrahim C; Haydin, Sertac; Onan, Ismihan S; Odemis, Ender; Bakir, Ihsan

2014-10-01

To investigate the efficacy of dornase alpha, a mucolytic agent, in children who developed pulmonary atelectasis after congenital heart surgery. Retrospective case-control study. Paediatric cardiac intensive care unit at a tertiary care hospital. Between July, 2011 and July, 2012, 41 patients who underwent congenital cardiac operations and developed post-operative pulmonary atelectasis that was resistant to conventional treatment and chest physiotherapy. In all, 26 patients received dornase alpha treatment. As a control group, 15 patients were treated with conventional medications and chest physiotherapy. The median age of patients was 25.5 (3-480) days in the study group and 50.0 (3-480) days in the control group. A total of 15 (57.6%) patients in the study group and 8 (53.3%) patients in the control group were male. The median weight was 4.2 (2.9-14.2) kg and 4.0 (3.5-13.6) kg in the study and control group, respectively. In the study group, pulmonary atelectasis was diagnosed at a median period of 5 (2-18) days after operations, whereas in the control group atelectasis was diagnosed at a median period of post-operative 6 (3-19) days. In the study group, the median atelectasis score decreased from 3.4 (1-6) to 0.8 (0-3) (p = 0.001). The median pO2 level increased from 69 (17-142) mmHg to 89 (30-168) mmHg (p = 0.04). In addition, heart rate and respiratory rate per minute were significantly decreased (p < 0.05). There were no significant changes in these parameters in the control group. The use of dornase alpha can be effective for the management of pulmonary atelectasis that develops following congenital heart surgery.

Dual developmental role of transcriptional regulator Ets1 in Xenopus cardiac neural crest vs. heart mesoderm

PubMed Central

Nie, Shuyi; Bronner, Marianne E.

2015-01-01

Aims Ets1 is an important transcription factor that is expressed in both the cardiac neural crest (NC) and heart mesoderm of vertebrate embryos. Moreover, Ets1 deletion in humans results in congenital heart abnormalities. To clarify the functional contributions of Ets1 in cardiac NC vs. heart mesoderm, we performed tissue-targeted loss-of-function analysis to compare the relative roles of Ets1 in these two tissues during heart formation using Xenopus embryos as a model system. Methods and results We confirmed by in situ hybridization analysis that Ets1 is expressed in NC and heart mesoderm during embryogenesis. Using a translation-blocking antisense morpholino to knockdown Ets1 protein selectively in the NC, we observed defects in NC delamination from the neural tube, collective cell migration, as well as segregation of NC streams in the cranial and cardiac regions. Many cardiac NC cells failed to reach their destination in the heart, resulting in defective aortic arch artery formation. A different set of defects was noted when Ets1 knockdown was targeted to heart mesoderm. The formation of the primitive heart tube was dramatically delayed and the endocardial tissue appeared depleted. As a result, the conformation of the heart was severely disrupted. In addition, the outflow tract septum was missing, and trabeculae formation in the ventricle was abolished. Conclusion Our study shows that Ets1 is required in both the cardiac NC and heart mesoderm, albeit for different aspects of heart formation. Our results reinforce the suggestion that proper interaction between these tissues is critical for normal heart development. PMID:25691536

Involvement of systemic venous congestion in heart failure.

PubMed

Rubio Gracia, J; Sánchez Marteles, M; Pérez Calvo, J I

2017-04-01

Systemic venous congestion has gained significant importance in the interpretation of the pathophysiology of acute heart failure, especially in the development of renal function impairment during exacerbations. In this study, we review the concept, clinical characterisation and identification of venous congestion. We update current knowledge on its importance in the pathophysiology of acute heart failure and its involvement in the prognosis. We pay special attention to the relationship between abdominal congestion, the pulmonary interstitium as filtering membrane, inflammatory phenomena and renal function impairment in acute heart failure. Lastly, we review decongestion as a new therapeutic objective and the measures available for its assessment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Left cardiac isomerism in the Sonic hedgehog null mouse.

PubMed

Hildreth, Victoria; Webb, Sandra; Chaudhry, Bill; Peat, Jonathan D; Phillips, Helen M; Brown, Nigel; Anderson, Robert H; Henderson, Deborah J

2009-06-01

Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from the loss of the effects of Shh in the establishment of laterality, combined with a reduced contribution made by cells derived from the second heart field.

Implementing a Graduate Certificate Program in Cardiovascular Epidemiology: The Jackson Heart Study

PubMed Central

Campbell Jenkins, Brenda W.; Addison, Clifton; Wilson, Gregory; Young, Lavon; Fields, Regina; Woodberry, Clevette; Payton, Marinelle

2015-01-01

The Jackson Heart Study (JHS) is committed to providing opportunities for expanding the understanding of the epidemiology, diagnosis, prevention, and treatment of cardiovascular diseases. The JHS Graduate Training and Education Center (GTEC) has initiated the Daniel Hale Williams Scholar (DHWS) program where students are afforded the opportunity to interact with epidemiologists and other biomedical scientists to learn to identify, predict, and prevent cardiovascular disease using the Jackson Heart Study data. This study describes the structured programs developed by JHS GTEC seeking to alleviate the shortage of trained professionals in cardiovascular epidemiology by training graduate students while they complete their academic degrees. The DHWS program provides: (1) an enrichment curriculum; (2) a learning community; (3) quarterly seminars; and (4) a Summer Institute. Students attend enrichment activities comprising: (1) Applied Biostatistics; (2) Cardiovascular Disease Epidemiology; (3) Social Epidemiology; (4) Emerging Topics; and (5) Research Writing. Training focuses on developing proficiency in cardiovascular health knowledge. The DHWS program is a unique strategy for incorporating rigorous academic and career-focused training to graduate students and has enabled the acquisition of competencies needed to impact cardiovascular disease management programs. PMID:26703701

[Pulse wave velocity as an early marker of diastolic heart failure in patients with hypertension].

PubMed

Moczulska, Beata; Kubiak, Monika; Bryczkowska, Anna; Malinowska, Ewa

2017-04-21

According to the WHO, hypertension is one of the major causes of death worldwide. It leads to a number of severe complications. Diastolic heart failure, that is heart failure with preserved ejection fraction (HFPEF), is especially common. New, but simple, indices for the early detection of patients who have not yet developed complications or are in their early developmental stages are still searched for. The aim of this study is to examine the correlation between pulse wave velocity (PWV) and markers of diastolic heart failure (DHF) assessed in echocardiography in patients with hypertension and no symptoms of heart failure. The study was comprised of 65 patients with treated hypertension. Patients with symptoms of heart failure, those with diabetes and smokers were excluded. Arterial stiffness was measured with the Mobil-O-Graph NG PWA. Pulse wave velocity (PWV) was estimated. The following markers of diastolic heart failure were assessed in the echocardiographic examination: E/A ratio - the ratio of the early (E) to late (A) ventricular filling velocities, DT - decceleration time, E/E' - the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity E' in tissue Doppler echocardiography. PWV was statistically significantly higher in the DHF group. In the group of patients with heart failure, the average E/A ratio was significantly lower as compared to the group with no heart failure. Oscillometric measurement of pulse wave velocity is non-invasive, lasts a few minutes and does not require the presence of a specialist. It allows for an early detection of patients at risk of diastolic heart failure even within the conditions of primary health care.

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function

PubMed Central

Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Das, Dipankar; Suresh, Mavanur R.; Falck, John R.; Graves, Joan P.; Zeldin, Darryl C.; Seubert, John M.

2009-01-01

Aims This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null). Methods and results Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C ε and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3β was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts. Conclusion Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events. PMID:19401302

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.

Comparing Asian American Women's Knowledge, Self-Efficacy, and Perceived Risk of Heart Attack to Other Racial and Ethnic Groups: The mPED Trial.

PubMed

Fukuoka, Yoshimi; Lisha, Nadra E; Vittinghoff, Eric

2017-09-01

The aim of the study was to compare knowledge and awareness of heart attacks/heart disease and perceived risk for future heart attack in Asian/Pacific Islander women, compared to other racial and ethnic groups. In this cross-sectional study, 318 women enrolled in a mobile phone-based physical activity education trial were analyzed. Heart attack knowledge, self-efficacy for recognizing and responding to heart attack symptoms, and perceived risk for a future heart attack were measured. Analyses were conducted using logistic, proportional odds, and linear regression models, depending on the outcome and adjusting for age. Pairwise differences between Asian/Pacific Islanders and the other four groups were assessed using a Bonferroni correction (p < 0.0125). Asian/Pacific Islander women had significantly lower total scores for knowledge of heart attack and self-efficacy for heart attack recognition and care seeking behavior compared to the Caucasian women (p = 0.001 and p = 0.002, respectively). However, perceived risk did not differ among the groups. Forty-six percent of the Asian American women, compared to 25% of Caucasian women, falsely believed "breast cancer is the number one cause of death for women (p = 0.002)." In addition, Asian/Pacific Islander women were less likely to report "arm pain, numbness, tingling, or radiating" as one of the heart attack symptoms compared to the Caucasian and the multiracial group (34%, 63% [p < 0.001], and 66% [p = 0.004], respectively). These findings highlight the urgent need to develop effective, tailored campaigns to close the knowledge gap between Asian/Pacific Islander women and Caucasian women.

Septum primum atrial septal defect in an infant with hypoplastic left heart syndrome.

PubMed

Loar, Robert W; Burkhart, Harold M; Taggart, Nathaniel W

2014-08-01

Hypoplastic left heart syndrome (HLHS) is a form of congenital heart disease characterized by severe underdevelopment of the left heart, leading to inadequate systemic blood flow. Several different atrial septal morphologies are observed in HLHS, most commonly a secundum atrial septal defect, patent foramen ovale, intact septum, and leftward displacement of the superior attachment of the septum primum. It has been postulated that atrial septal development is associated with the development of the left heart. We present a case of a newborn infant with HLHS and the unusual finding of a primum ASD.

A new generation of high flex life polyurethane urea for polymer heart valve--studies on in vivo biocompatibility and biodurability.

PubMed

Thomas, Vinoy; Jayabalan, Muthu

2009-04-01

Development of new generation high flex life polyurethane urea (HFL18-PU) with appropriate elastic modulus, biocompatibility, blood compatibility, resistant to calcification, and biodurability for the long-term use as cardiac device is still a challenge. This study reports the development of a fully aliphatic, ether-free physically cross-linked and low elastic modulus (6.841 +/- 0.27 MPa) polyurethane urea having in vivo biostability, in vivo biocompatibility and high flex-life (721 +/- 30 million cycles) that can satisfy the requirements for the fabrication of tri-leaflet heart valve. Copyright 2008 Wiley Periodicals, Inc.

[Chronic heart failure and depression].

PubMed

Herrmann-Lingen, C

2018-05-01

Depression is a frequent comorbidity in chronic heart failure. It can be triggered by the experience of suffering from heart disease, but it can also play a causal role in accelerated development and poor prognosis of heart failure. The aim of this study was to investigate the interrelationships between heart failure and depression and the psychophysiological and behavioral mechanisms involved in this association. The effects of comorbid depression on quality of life in patients with heart failure were also examined and therapeutic options reviewed. A narrative review of the literature was undertaken. Several psychophysiological and behavioral mechanisms have been identified as mediators of the association between depression and heart failure and the adverse prognostic effects of this comorbidity. Comorbid depression leads to substantial reductions in health-related quality of life. These effects are only incompletely antagonized by exercise training and cognitive behavioral therapy. No specific effect of antidepressant medication has been demonstrated as yet in patients with heart failure. While current guidelines recommend the identification and treatment of depressive comorbidity in patients with heart failure, the available evidence provides no convincing rationale for specific treatment recommendations beyond the guideline-based treatment of heart failure itself, lifestyle interventions and patient-centered medical care. If available, psychotherapy should be offered, ideally cognitive behavioral therapy. For patients that do not improve sufficiently under outpatient treatment, the German health care system offers dedicated psychocardiological inpatient treatment programs.

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.

Cardiac responses to hypoxia and reoxygenation in Drosophila.

PubMed

Zarndt, Rachel; Piloto, Sarah; Powell, Frank L; Haddad, Gabriel G; Bodmer, Rolf; Ocorr, Karen

2015-12-01

An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-α), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation. Copyright © 2015 the American Physiological Society.

Dextrocardia

MedlinePlus

Cyanotic heart defect - dextrocardia; Congenital heart defect - dextrocardia; Birth defect - dextrocardia ... During the early weeks of pregnancy, the baby’s heart develops. Sometimes, it turns so that it points ...

Recent advances in understanding and prevention of sudden cardiac death

PubMed Central

Vandenberg, Jamie I.; Perry, Matthew D.; Hill, Adam P.

2017-01-01

There have been tremendous advances in the diagnosis and treatment of heart disease over the last 50 years. Nevertheless, it remains the number one cause of death. About half of heart-related deaths occur suddenly, and in about half of these cases the person was unaware that they had underlying heart disease. Genetic heart disease accounts for only approximately 2% of sudden cardiac deaths, but as it typically occurs in younger people it has been a particular focus of activity in our quest to not only understand the underlying mechanisms of cardiac arrhythmogenesis but also develop better strategies for earlier detection and prevention. In this brief review, we will highlight trends in the recent literature focused on sudden cardiac death in genetic heart diseases and how these studies are contributing to a broader understanding of sudden death in the community. PMID:29026525

Risk model of prolonged intensive care unit stay in Chinese patients undergoing heart valve surgery.

PubMed

Wang, Chong; Zhang, Guan-xin; Zhang, Hao; Lu, Fang-lin; Li, Bai-ling; Xu, Ji-bin; Han, Lin; Xu, Zhi-yun

2012-11-01

The aim of this study was to develop a preoperative risk prediction model and an scorecard for prolonged intensive care unit length of stay (PrlICULOS) in adult patients undergoing heart valve surgery. This is a retrospective observational study of collected data on 3925 consecutive patients older than 18 years, who had undergone heart valve surgery between January 2000 and December 2010. Data were randomly split into a development dataset (n=2401) and a validation dataset (n=1524). A multivariate logistic regression analysis was undertaken using the development dataset to identify independent risk factors for PrlICULOS. Performance of the model was then assessed by observed and expected rates of PrlICULOS on the development and validation dataset. Model calibration and discriminatory ability were analysed by the Hosmer-Lemeshow goodness-of-fit statistic and the area under the receiver operating characteristic (ROC) curve, respectively. There were 491 patients that required PrlICULOS (12.5%). Preoperative independent predictors of PrlICULOS are shown with odds ratio as follows: (1) age, 1.4; (2) chronic obstructive pulmonary disease (COPD), 1.8; (3) atrial fibrillation, 1.4; (4) left bundle branch block, 2.7; (5) ejection fraction, 1.4; (6) left ventricle weight, 1.5; (7) New York Heart Association class III-IV, 1.8; (8) critical preoperative state, 2.0; (9) perivalvular leakage, 6.4; (10) tricuspid valve replacement, 3.8; (11) concurrent CABG, 2.8; and (12) concurrent other cardiac surgery, 1.8. The Hosmer-Lemeshow goodness-of-fit statistic was not statistically significant in both development and validation dataset (P=0.365 vs P=0.310). The ROC curve for the prediction of PrlICULOS in development and validation dataset was 0.717 and 0.700, respectively. We developed and validated a local risk prediction model for PrlICULOS after adult heart valve surgery. This model can be used to calculate patient-specific risk with an equivalent predicted risk at our centre in future clinical practice. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

PubMed

DiPietro, Janet A; Costigan, Kathleen A; Voegtline, Kristin M

2015-09-01

Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new technologies portend an era of accelerated discovery of the earliest period of development

The hippo pathway in heart development, regeneration, and diseases.

PubMed

Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

2015-04-10

The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. © 2015 American Heart Association, Inc.

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function.

PubMed

Sarmah, Swapnalee; Marrs, James A

2016-12-16

Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed.

Health condition and familial factors associated with health-related quality of life in adolescents with congenital heart disease: a cross sectional study.

PubMed

Im, Yu-Mi; Yun, Tae-Jin; Lee, Sunhee

2018-01-10

The focus of clinical care after the repair of congenital heart disease has shifted from saving life of the patient to the patient's quality of life. The purpose of this study was to examine the health condition and familial factors associated with the health related quality of life of adolescents with congenital heart disease. Ninety-eight adolescents aged 13-19 years were collected from a congenital heart clinic from July 22 to August 23, 2013. Perceptions of parental rearing behaviors, health related quality of life of adolescent with congenital heart disease, and general characteristics were measured. We used multiple linear regression analysis to explore factors that are associated with the health related quality of life of adolescents with congenital heart disease. New York heart association class (Adj R 2  = .186, p = .000), presence of siblings (Adj R 2  = .240, p = .010), and mother's emotional warmth (Adj R 2  = .265, p = .043) were significantly associated with the health related quality of life of adolescents with congenital heart disease. Emotionally warm parental rearing behaviors and the presence of siblings were important familial factors that were positively associated with HRQOL in adolescents with CHD. Therefore, it is important for healthcare providers to develop a greater sensitivity to, and awareness of, the familial influences that may be impacting a subject's HRQOL, as well as the exigencies of the CHD, itself.

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth

PubMed Central

Kimball, Todd; Rasmussen, Tara L.; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R.; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O.; Vondriska, Thomas M.

2016-01-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. PMID:27663768

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth.

PubMed

Franklin, Sarah; Kimball, Todd; Rasmussen, Tara L; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O; Vondriska, Thomas M

2016-11-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. Copyright © 2016 the American Physiological Society.

Optimising self-care support for people with heart failure and their caregivers: development of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention using intervention mapping.

PubMed

Greaves, Colin J; Wingham, Jennifer; Deighan, Carolyn; Doherty, Patrick; Elliott, Jennifer; Armitage, Wendy; Clark, Michelle; Austin, Jackie; Abraham, Charles; Frost, Julia; Singh, Sally; Jolly, Kate; Paul, Kevin; Taylor, Louise; Buckingham, Sarah; Davis, Russell; Dalal, Hasnain; Taylor, Rod S

2016-01-01

We aimed to establish the support needs of people with heart failure and their caregivers and develop an intervention to improve their health-related quality of life. We used intervention mapping to guide the development of our intervention. We identified "targets for change" by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We then used behaviour change theory, expert opinion and a taxonomy of behaviour change techniques, to identify barriers to and facilitators of change and to match intervention strategies to each target. A patient and public involvement group helped to identify patient and caregiver needs, refine the intervention objectives and strategies and deliver training to the intervention facilitators. A feasibility study (ISRCTN25032672) involving 23 patients, 12 caregivers and seven trained facilitators at four sites assessed the feasibility and acceptability of the intervention and quality of delivery and generated ideas to help refine the intervention. The Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention is a comprehensive self-care support programme comprising the "Heart Failure Manual", a choice of two exercise programmes for patients, a "Family and Friends Resource" for caregivers, a "Progress Tracker" tool and a facilitator training course. The main targets for change are engaging in exercise training, monitoring for symptom deterioration, managing stress and anxiety, managing medications and understanding heart failure. Secondary targets include managing low mood and smoking cessation. The intervention is facilitated by trained healthcare professionals with specialist cardiac experience over 12 weeks, via home and telephone contacts. The feasibility study found high levels of satisfaction and engagement with the intervention from facilitators, patients and caregivers. Intervention fidelity analysis and stakeholder feedback suggested that there was room for improvement in several areas, especially in terms of addressing caregivers' needs. The REACH-HF materials were revised accordingly. We have developed a comprehensive, evidence-informed, theoretically driven self-care and rehabilitation intervention that is grounded in the needs of patients and caregivers. A randomised controlled trial is underway to assess the effectiveness and cost-effectiveness of the REACH-HF intervention in people with heart failure and their caregivers.

Sleep Quality, Sleep Duration, and the Risk of Coronary Heart Disease: A Prospective Cohort Study With 60,586 Adults.

PubMed

Lao, Xiang Qian; Liu, Xudong; Deng, Han-Bing; Chan, Ta-Chien; Ho, Kin Fai; Wang, Feng; Vermeulen, Roel; Tam, Tony; Wong, Martin C S; Tse, L A; Chang, Ly-Yun; Yeoh, Eng-Kiong

2018-01-15

There is limited information on the relationship between risk of cardiovascular disease and the joint effects of sleep quality and sleep duration, especially from large, prospective, cohort studies. This study is to prospectively investigate the joint effects of sleep quality and sleep duration on the development of coronary heart disease. This study examined 60,586 adults aged 40 years or older. A self-administered questionnaire was used to collect information on sleep quality and sleep duration as well as a wide range of potential confounders. Events of coronary heart disease were self-reported in subsequent medical examinations. Two types of Sleep Score (multiplicative and additive) were constructed to reflect the participants' sleep profiles, considering both sleep quality and sleep duration. The Cox regression model was used to estimate the hazard ratio (HR) and the 95% confidence interval (CI). A total of 2,740 participants (4.5%) reported new events of coronary heart disease at follow-up. For sleep duration, participants in the group of < 6 h/d was significantly associated with an increased risk of coronary heart disease (HR: 1.13, 95% CI: 1.04-1.23). However, the association in the participants with long sleep duration (> 8 h/d) did not reach statistical significance (HR: 1.11, 95% CI: 0.98-1.26). For sleep quality, both dreamy sleep (HR: 1.21, 95% CI: 1.10-1.32) and difficult to fall asleep/use of sleeping pills or drugs (HR: 1.40, 95% CI: 1.25-1.56) were associated with an increased risk of the disease. Participants in the lowest quartile of multiplicative Sleep Score (HR: 1.31, 95% CI: 1.16-1.47) and of additive sleep score (HR: 1.31, 95% CI: 1.16-1.47) were associated with increased risk of coronary heart disease compared with those in the highest quartile. Both short sleep duration and poor sleep quality are associated with the risk of coronary heart disease. The association for long sleep duration does not reach statistical significance. Lower Sleep Score (poorer sleep profile) increases the risk of coronary heart disease, suggesting the importance of considering sleep duration and sleep quality together when developing strategies to improve sleep for cardiovascular disease prevention. © 2018 American Academy of Sleep Medicine

Persistent high serum bicarbonate and the risk of heart failure in patients with chronic kidney disease (CKD): A report from the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Dobre, Mirela; Yang, Wei; Pan, Qiang; Appel, Lawrence; Bellovich, Keith; Chen, Jing; Feldman, Harold; Fischer, Michael J; Ham, L L; Hostetter, Thomas; Jaar, Bernard G; Kallem, Radhakrishna R; Rosas, Sylvia E; Scialla, Julia J; Wolf, Myles; Rahman, Mahboob

2015-04-20

Serum bicarbonate varies over time in chronic kidney disease (CKD) patients, and this variability may portend poor cardiovascular outcomes. The aim of this study was to conduct a time-updated longitudinal analysis to evaluate the association of serum bicarbonate with long-term clinical outcomes: heart failure, atherosclerotic events, renal events (halving of estimated glomerular filtration rate [eGFR] or end-stage renal disease), and mortality. Serum bicarbonate was measured annually, in 3586 participants with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Marginal structural models were created to allow for integration of all available bicarbonate measurements and proper adjustment for time-dependent confounding. During the 6 years follow-up, 512 participants developed congestive heart failure (26/1000 person-years) and 749 developed renal events (37/1000 person-years). The risk of heart failure and death was significantly higher for participants who maintained serum bicarbonate >26 mmol/L for the entire duration of follow-up (hazard ratio [HR] 1.66; 95% confidence interval [CI], 1.23 to 2.23, and HR 1.36, 95% CI 1.02 to 1.82, respectively) compared with participants who kept their bicarbonate 22 to 26 mmol/L, after adjusting for demographics, co-morbidities, medications including diuretics, eGFR, and proteinuria. Participants who maintained serum bicarbonate <22 mmol/L had almost a 2-fold increased risk of renal disease progression (HR 1.97; 95% CI, 1.50 to 2.57) compared with participants with bicarbonate 22 to 26 mmol/L. In this large CKD cohort, persistent serum bicarbonate >26 mmol/L was associated with increased risk of heart failure events and mortality. Further studies are needed to determine the optimal range of serum bicarbonate in CKD to prevent adverse clinical outcomes. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Heart and skeletal muscle inflammation (HSMI) disease diagnosed on a British Columbia salmon farm through a longitudinal farm study

PubMed Central

Ferguson, Hugh W.; Schulze, Angela D.; Kaukinen, Karia H.; Li, Shaorong; Vanderstichel, Raphaël; Wessel, Øystein; Rimstad, Espen; Gardner, Ian A.; Hammell, K. Larry; Miller, Kristina M.

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is an emerging disease of marine-farmed Atlantic Salmon (Salmo salar), first recognized in 1999 in Norway, and later also reported in Scotland and Chile. We undertook a longitudinal study involving health evaluation over an entire marine production cycle on one salmon farm in British Columbia (Canada). In previous production cycles at this farm site and others in the vicinity, cardiac lesions not linked to a specific infectious agent or disease were identified. Histologic assessments of both live and moribund fish samples collected at the farm during the longitudinal study documented at the population level the development, peak, and recovery phases of HSMI. The fish underwent histopathological evaluation of all tissues, Twort’s Gram staining, immunohistochemistry, and molecular quantification in heart tissue of 44 agents known or suspected to cause disease in salmon. Our analysis showed evidence of HSMI histopathological lesions over an 11-month timespan, with the prevalence of lesions peaking at 80–100% in sampled fish, despite mild clinical signs with no associated elevation in mortalities reported at the farm level. Diffuse mononuclear inflammation and myodegeneration, consistent with HSMI, was the predominant histologic observation in affected heart and skeletal muscle. Infective agent monitoring identified three agents at high prevalence in salmon heart tissue, including Piscine orthoreovirus (PRV), and parasites Paranucleospora theridion and Kudoa thyrsites. However, PRV alone was statistically correlated with the occurrence and severity of histopathological lesions in the heart. Immunohistochemical staining further localized PRV throughout HSMI development, with the virus found mainly within red blood cells in early cases, moving into the cardiomyocytes within or, more often, on the periphery of the inflammatory reaction during the peak disease, and reducing to low or undetectable levels later in the production cycle. This study represents the first longitudinal assessment of HSMI in a salmon farm in British Columbia, providing new insights on the pathogenesis of the disease. PMID:28225783

Emotions, the meaning of food and heart failure: a grounded theory study.

PubMed

Jacobsson, Anna; Pihl, Emma; Mårtensson, Jan; Fridlund, Bengt

2004-06-01

Many patients with heart failure have generalized wasting, referred to as cardiac cachexia. This leads to skeletal muscle wasting, impaired mobility, reduced functional capacity and poor prognosis. Patients with heart failure have symptoms that can affect their food intake, for example breathing difficulties, fatigue, nausea, loss of appetite, early feeling of fullness and ascites. These dietary problems and patients' nutritional status, can be significantly improved by means of simple nursing interventions. This paper reports a grounded theory study which developed a theoretical model of experiences of food and food intake among patients with heart failure. A descriptive and exploratory design, with a grounded theory analysis, was used. Data were collected in 2002 through interviews with 11 patients with heart failure. Two core categories emerged: emotions and the meaning of food. Psychosocial meaning could be associated with positive feelings of well-being, or negative feelings of sorrow. Physiological meaning could be associated with positive feelings of comfort or negative feelings of burden. Patients' experiences of food and eating changed during the development of the disease. Feelings of fatigue and lack of appetite gave rise to a feeling of deprivation because of missing both eating and the related social environment. This could lead to a loss of personal identity. Although the findings of a qualitative study cannot be generalized, they raise important clinical nursing issues. With increasingly shorter hospital stays, these problems will need to be addressed by community healthcare staff and family carers. Therefore, all healthcare professionals need knowledge about heart disease and information techniques if they are to be able to give appropriate care to this group. Ignorance about food and eating can easily lead to malnourishment, with an increased risk of the patients falling into a vicious circle. Implications of the study for health care practice and research are identified.

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.

The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis.

PubMed

Van Den Berg, Patricia; Body, Richard

2018-03-01

The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3-29.1%) developed major adverse cardiac events after a mean of 6 weeks' follow-up. Among patients categorised as 'low risk' and suitable for early discharge (HEART score 0-3), the pooled incidence of 'missed' major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0-98.2%) and 47.0% (95% CI 41.0-53.5%), respectively. Patients with a HEART score of 0-3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are 'missed' by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

Rac1-PAK2 pathway is essential for zebrafish heart regeneration

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

Peng, Xiangwen; He, Quanze; Li, Guobao

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation duringmore » heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.« less

Understanding chronic heart failure

PubMed Central

Fenton, Matthew; Burch, Michael

2007-01-01

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality. PMID:17715446

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum

PubMed Central

Saburkina, Inga; Gukauskiene, Ligita; Rysevaite, Kristina; Brack, Kieran E; Pauza, Audrys G; Pauziene, Neringa; Pauza, Dainius H

2014-01-01

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517–2788; aged) vs. 2118 ± 108 (range 1513–2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well-developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans. PMID:24527844

Nonlinear Dynamical Analysis of Fibrillation

NASA Astrophysics Data System (ADS)

Kerin, John A.; Sporrer, Justin M.; Egolf, David A.

2013-03-01

The development of spatiotemporal chaotic behavior in heart tissue, termed fibrillation, is a devastating, life-threatening condition. The chaotic behavior of electrochemical signals, in the form of spiral waves, causes the muscles of the heart to contract in an incoherent manner, hindering the heart's ability to pump blood. We have applied the mathematical tools of nonlinear dynamics to large-scale simulations of a model of fibrillating heart tissue to uncover the dynamical modes driving this chaos. By studying the evolution of Lyapunov vectors and exponents over short times, we have found that the fibrillating tissue is sensitive to electrical perturbations only in narrow regions immediately in front of the leading edges of spiral waves, especially when these waves collide, break apart, or hit the edges of the tissue sample. Using this knowledge, we have applied small stimuli to areas of varying sensitivity. By studying the evolution of the effects of these perturbations, we have made progress toward controlling the electrochemical patterns associated with heart fibrillation. This work was supported by the U.S. National Science Foundation (DMR-0094178) and Research Corporation.

C-reactive protein and homocysteine levels are associated with abnormal heart rate recovery in women with polycystic ovary syndrome.

PubMed

Kaya, Cemil; Akgül, Ebru; Pabuccu, Recai

2010-06-01

To determine heart rate recovery (HRR) in patients with polycystic ovary syndrome (PCOS) and its relation to C-reactive protein (CRP) and homocysteine (Hcy) levels. Prospective clinical study. University hospital. Sixty-eight women with PCOS and 68 healthy women were included this study. Heart rate recovery was evaluated. We measured serum levels of CRP and Hcy. The presence of insulin resistance was investigated using homeostasis model assesment (HOMA-IR). Heart rate recovery, CRP, Hcy. Heart rate recovery was significantly decreased in women with PCOS compared with control group women. Subjects with abnormal HRR had significantly greater levels of CRP and Hcy. The PCOS patients with HRR in the top tertile compared with the bottom quartile tended to have lower mean CRP and Hcy levels. The HRR was significantly and negatively correlated with age, CRP, Hcy, HOMA-IR, and body mass index. C-reactive protein and Hcy are independent determinants of HRR. The CRP and Hcy levels may affect the development and progression of abnormal HRR in PCOS. Crown Copyright (c) 2010. Published by Elsevier Inc. All rights reserved.

The Penn State Heart Assistant: A pilot study of a web-based intervention to improve self-care of heart failure patients.

PubMed

Lloyd, Tom; Buck, Harleah; Foy, Andrew; Black, Sara; Pinter, Antony; Pogash, Rosanne; Eismann, Bobby; Balaban, Eric; Chan, John; Kunselman, Allen; Smyth, Joshua; Boehmer, John

2017-05-01

The Penn State Heart Assistant, a web-based, tablet computer-accessed, secure application was developed to conduct a proof of concept test, targeting patient self-care activities of heart failure patients including daily medication adherence, weight monitoring, and aerobic activity. Patients (n = 12) used the tablet computer-accessed program for 30 days-recording their information and viewing a short educational video. Linear random coefficient models assessed the relationship between weight and time and exercise and time. Good medication adherence (66% reporting taking 75% of prescribed medications) was reported. Group compliance over 30 days for weight and exercise was 84 percent. No persistent weight gain over 30 days, and some indication of weight loss (slope of weight vs time was negative (-0.17; p value = 0.002)), as well as increased exercise (slope of exercise vs time was positive (0.08; p value = 0.04)) was observed. This study suggests that mobile technology is feasible, acceptable, and has potential for cost-effective opportunities to manage heart failure patients safely at home.

Toxicity and cardiac effects of carbaryl in early developing zebrafish (Danio rerio) embryos

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

Lin, C.C.; Hui, Michelle N.Y.; Cheng, S.H. E-mail: bhcheng@cityu.edu.hk

2007-07-15

Carbaryl, an acetylcholinesterase inhibitor, is known to be moderately toxic to adult zebrafish and has been reported to cause heart malformations and irregular heartbeat in medaka. We performed experiments to study the toxicity of carbaryl, specifically its effects on the heart, in early developing zebrafish embryos. LC50 and EC50 values for carbaryl at 28 h post-fertilization were 44.66 {mu}g/ml and 7.52 {mu}g/ml, respectively, and 10 {mu}g/ml carbaryl was used in subsequent experiments. After confirming acetylcholinesterase inhibition by carbaryl using an enzymatic method, we observed red blood cell accumulation, delayed hatching and pericardial edema, but not heart malformation as described inmore » some previous reports. Our chronic exposure data also demonstrated carbaryl-induced bradycardia, which is a common effect of acetylcholinesterase inhibitors due to the accumulation of acetylcholine, in embryos from 1 day post-fertilization (dpf) to 5 dpf. The distance between the sinus venosus, the point where blood enters the atrium, and the bulbus arteriosus, the point where blood leaves the ventricle, indicated normal looping of the heart tube. Immunostaining of myosin heavy chains with the ventricle-specific antibody MF20 and the atrium-specific antibody S46 showed normal development of heart chambers. At the same time, acute exposure resulted in carbaryl-induced bradycardia. Heart rate dropped significantly after a 10-min exposure to 100 {mu}g/ml carbaryl but recovered when carbaryl was removed. The novel observation of carbaryl-induced bradycardia in 1- and 2-dpf embryos suggested that carbaryl affected cardiac function possibly through an alternative mechanism other than acetylcholinesterase inhibition such as inhibition of calcium ion channels, since acetylcholine receptors in zebrafish are not functional until 3 dpf. However, the exact nature of this mechanism is currently unknown, and thus further studies are required.« less

Does Mindfulness Improve After Heart Coherence Training in Patients With Chronic Musculoskeletal Pain and Healthy Subjects? A Pilot Study.

PubMed

Soer, Remko; de Jong, Annemieke B; Hofstra, Bert L; Preuper, Henrica R Schiphorst; Reneman, Michiel F

2015-07-01

Mindfulness and heart coherence training (HCT) training are applied increasingly in the treatment of patients with chronic musculoskeletal pain (CMP). Questionnaires have been developed to assess changes in mindfulness but no gold standard is available. Explore the relationship between changes in mindfulness scores and changes in heart coherence after 3 sessions of HCT in patients with CMP and in healthy subjects. Ten patients with CMP and 15 healthy subjects were trained in self-regulation with the use of HCT following a standardized stress relief program developed by the HeartMath Institute. A heart coherence-score (HC-score) was constructed with scores ranging from 0-100 with higher scores reflecting more heart rate variability (HRV) coherency. Change scores, Spearman correlation coefficients, and Wilcoxon Signed Rank test were calculated to test relationships and differences between HC-score, the Mindfulness Attention and Awareness Scale (MAAS) and Five Facet Mindfulness Questionnaire (FFMQ). A new questionnaire was constructed to explore on which mindfulness-related domains patients with CMP report changes after HCT. Increases were present on HC-score in healthy subjects (P<.01) and in patients (P<.01) between baseline and follow-up. Effect sizes on change on the MAAS and FFMQ were low. Weak (r<0.25) and non-significant correlations were observed in change scores between HC-score and MAAS or FFMQ. Patients reported significant favorable differences on 6 mindfulness related domains in the new questionnaire: breathing rhythm, physical awareness, positive or negative emotions, recognition of stressful situations, thoughts, and tendency to actively self-regulate. In this pilot study, mindfulness as assessed by the MAAS and FFMQ does not appear to improve after HCT. HRV coherency, MAAS, and FFMQ measure different constructs and are weakly related. It is of great importance to choose and develop valid measures that reflect patients' states of mindfulness. Content and face validity of measures of mindfulness may be considered in the light of performance-based measures.

Carcinoid heart disease: Diagnosis and management.

PubMed

Luis, Sushil A; Pellikka, Patricia A

2016-01-01

Hedinger syndrome refers to carcinoid valvular heart disease. The disease is believed to be triggered by vasoactive substances that result in valvular fibrosis. It classically occurs in patients with metastatic carcinoid and preferentially involves the right sided cardiac valves. Affected valves become thickened and retracted, exhibiting regurgitation and sometimes, stenosis. Echocardiography is recommended in patients with carcinoid syndrome and a follow up study is advisable in those who develop a murmur or other symptoms or signs of valvular heart disease. For appropriately selected patients, valve replacement surgery appears to improve outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer Survivors’ Health Worries and Associations with Lifestyle Practices

PubMed Central

Mosher, Catherine E.; Lipkus, Isaac M.; Sloane, Richard; Kraus, William E.; Snyder, Denise Clutter; Peterson, Bercedis; Jones, Lee W.; Demark-Wahnefried, Wendy

2013-01-01

This study examined among recently diagnosed breast and prostate cancer survivors (N = 678) associations between worry about a future diagnosis of heart disease or cancer and hypothetical and actual adherence to exercise and dietary guidelines. Greater worry about future illness was reported under the hypothetical scenario of non-adherence to guidelines relative to the scenario of adherence. Worry about potential heart disease was associated with actual adherence to guidelines, whereas worry about a potential cancer diagnosis was not. Findings suggest that the motivational properties of worry should be considered when developing interventions to reduce heart disease risk among cancer survivors. PMID:18987083

Heart rate variability as determinism with jump stochastic parameters.

PubMed

Zheng, Jiongxuan; Skufca, Joseph D; Bollt, Erik M

2013-08-01

We use measured heart rate information (RR intervals) to develop a one-dimensional nonlinear map that describes short term deterministic behavior in the data. Our study suggests that there is a stochastic parameter with persistence which causes the heart rate and rhythm system to wander about a bifurcation point. We propose a modified circle map with a jump process noise term as a model which can qualitatively capture such this behavior of low dimensional transient determinism with occasional (stochastically defined) jumps from one deterministic system to another within a one parameter family of deterministic systems.

Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

PubMed

Soncini, Emanuele; Paganelli, Simone; Vezzani, Cristina; Gargano, Giancarlo; Giovanni Battista, La Sala

2014-09-01

To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥ 37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. The mean values of pH and base excess decreased proportionally as tracings worsened (p < 0.001). The duration of at least 30 min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤-12 mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50 min. Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling.

PubMed

Li, Y Y; McTiernan, C F; Feldman, A M

2000-05-01

Myocardial fibrosis due to maladaptive extracellular matrix remodeling contributes to dysfunction of the failing heart. Further elucidation of the mechanism by which myocardial fibrosis and dilatation can be prevented or even reversed remains of great interest as a potential means to limit myocardial remodeling and dysfunction. Matrix metalloproteinases (MMPs) are the driving force behind extracellular matrix degradation during remodeling and are increased in the failing human heart. MMPs are regulated by a variety of growth factors, cytokines, and matrix fragments such as matrikines. In the present report, we discuss the regulation of MMPs, the role of MMPs in the development of cardiac fibrosis, and the modulation of MMP activity using gene transfer and knockout technologies. We also present recent findings from our laboratory on the regulation of the extracellular MMP inducer (EMMPRIN), MMPs, and transforming growth factor-beta(1) in the failing human heart before and after left ventricular assist device support, as well as the possibility of preventing ventricular fibrosis using different anti-MMP strategies. Several studies suggest that such modulation of MMP activity can alter ventricular remodeling, myocardial dysfunction, and the progression of heart failure. It is therefore suggested that the interplay of MMPs and their regulators is important in the development of the heart failure phenotype, and myocardial fibrosis in heart failure may be modified by modulating MMP activity.

Prevention by cromakalim of spontaneously occurring cardiac necroses in polymyopathic hamsters.

PubMed

Jasmin, G; Proschek, L

1996-11-01

Previous studies on the heart necrotizing process at early stages of the hamster polymyopathy have led us to believe that this hereditary disease derives from a defective transmembrane ion flux resulting in myocardial Ca2+ over-load. On the other hand, certain K+ ATP channel openers were shown to prevent cytosolic Ca2+ accumulation in ischemic hearts. Therefore, we investigated the potential beneficial effect of chronic treatment with cromakalim (CR) on the development of necrotic changes in hamster myopathic hearts. Young cardiomyopathic (CM) hamsters were treated parenterally with CR over 4 consecutive weeks. The K+ ATP opener was dissolved in 5% DMSO and injected twice daily (s.c. and i.p. alternatively) at a dose level of 2.5 mg/kg per injection. Microscopic readings were carried out in staged serial paraffin sections of heart ventricles, the diaphragm, and tongue, will all tissues freshly taken at autopsy. In comparison with control untreated hearts, which exhibit numerous necrotic calcific foci, only minute myolytic lesions were found in 5 of 12 hamsters hearts receiving CR (p < 0.0001). Interestingly, the dystrophic process in the tongue was significantly less severe (p < 0.0004) in CR-treated animals. These observations provide evidence for the first time that in vivo sustained treatment with a K+ ATP opener exerts cardioprotection upon development of the hamster hereditary cardiomyopathy.

Ventricular septal defect

MedlinePlus

... causing an irregular or slow heart rhythm) Delayed growth and development ( failure to thrive in infancy) Heart failure Infective endocarditis (bacterial infection of the heart) Pulmonary hypertension (high blood ...

Sleep Quality, Sleep Duration, and the Risk of Coronary Heart Disease: A Prospective Cohort Study With 60,586 Adults

PubMed Central

Lao, Xiang Qian; Liu, Xudong; Deng, Han-Bing; Chan, Ta-Chien; Ho, Kin Fai; Wang, Feng; Vermeulen, Roel; Tam, Tony; Wong, Martin C.S.; Tse, L.A.; Chang, Ly-yun; Yeoh, Eng-Kiong

2018-01-01

Study Objectives: There is limited information on the relationship between risk of cardiovascular disease and the joint effects of sleep quality and sleep duration, especially from large, prospective, cohort studies. This study is to prospectively investigate the joint effects of sleep quality and sleep duration on the development of coronary heart disease. Methods: This study examined 60,586 adults aged 40 years or older. A self-administered questionnaire was used to collect information on sleep quality and sleep duration as well as a wide range of potential confounders. Events of coronary heart disease were self-reported in subsequent medical examinations. Two types of Sleep Score (multiplicative and additive) were constructed to reflect the participants' sleep profiles, considering both sleep quality and sleep duration. The Cox regression model was used to estimate the hazard ratio (HR) and the 95% confidence interval (CI). Results: A total of 2,740 participants (4.5%) reported new events of coronary heart disease at follow-up. For sleep duration, participants in the group of < 6 h/d was significantly associated with an increased risk of coronary heart disease (HR: 1.13, 95% CI: 1.04–1.23). However, the association in the participants with long sleep duration (> 8 h/d) did not reach statistical significance (HR: 1.11, 95% CI: 0.98–1.26). For sleep quality, both dreamy sleep (HR: 1.21, 95% CI: 1.10–1.32) and difficult to fall asleep/use of sleeping pills or drugs (HR: 1.40, 95% CI: 1.25–1.56) were associated with an increased risk of the disease. Participants in the lowest quartile of multiplicative Sleep Score (HR: 1.31, 95% CI: 1.16–1.47) and of additive sleep score (HR: 1.31, 95% CI: 1.16–1.47) were associated with increased risk of coronary heart disease compared with those in the highest quartile. Conclusions: Both short sleep duration and poor sleep quality are associated with the risk of coronary heart disease. The association for long sleep duration does not reach statistical significance. Lower Sleep Score (poorer sleep profile) increases the risk of coronary heart disease, suggesting the importance of considering sleep duration and sleep quality together when developing strategies to improve sleep for cardiovascular disease prevention. Citation: Lao XQ, Liu X, Deng HB, Chan TC, Ho KF, Wang F, Vermeulen R, Tam T, Wong MC, Tse LA, Chang LY, Yeoh EK. Sleep quality, sleep duration, and the risk of coronary heart disease: a prospective cohort study with 60,586 adults. J Clin Sleep Med. 2018;14(1):109–117. PMID:29198294

Dynamic Imaging of Mouse Embryos and Cardiodynamics in Static Culture.

PubMed

Lopez, Andrew L; Larina, Irina V

2018-01-01

The heart is a dynamic organ that quickly undergoes morphological and mechanical changes through early embryonic development. Characterizing these early moments is important for our understanding of proper embryonic development and the treatment of heart disease. Traditionally, tomographic imaging modalities and fluorescence-based microscopy are excellent approaches to visualize structural features and gene expression patterns, respectively, and connect aberrant gene programs to pathological phenotypes. However, these approaches usually require static samples or fluorescent markers, which can limit how much information we can derive from the dynamic and mechanical changes that regulate heart development. Optical coherence tomography (OCT) is unique in this circumstance because it allows for the acquisition of three-dimensional structural and four-dimensional (3D + time) functional images of living mouse embryos without fixation or contrast reagents. In this chapter, we focus on how OCT can visualize heart morphology at different stages of development and provide cardiodynamic information to reveal mechanical properties of the developing heart.

Sleep-Disordered Breathing in Patients with Pulmonary Valve Incompetence Complicating Congenital Heart Disease.

PubMed

Miles, Susan; Ahmad, Waheed; Bailey, Amy; Hatton, Rachael; Boyle, Andrew; Collins, Nicholas

2016-12-01

Long standing pulmonary regurgitation results in deleterious effects on right heart size and function with late consequences of right heart volume overload including ventricular dilatation, propensity to arrhythmia and right heart failure. As sleep disordered breathing may predispose to elevations in pulmonary vascular resistance and associated negative effects on right ventricular function, we sought to assess this in patients with underlying congenital heart disease. We performed a pilot study to evaluate the incidence of sleep-disordered breathing in a patient population with a history of long standing pulmonary valve incompetence in patients with congenital heart disease using overnight oximetry. Patients with a background of tetralogy of Fallot repair or residual pulmonary incompetence following previous pulmonary valve intervention for congenital pulmonary stenosis were included. Twenty-two patients underwent overnight oximetry. The mean age of the cohort was 34.3 ± 15.2 years with no patients observed to have severe underlying pulmonary hypertension. Abnormal overnight oximetry was seen in 13/22 patients (59.1%) with 2/22 (9.1%) patients considered to have severe abnormalities. An important proportion of patients with a background of pulmonary incompetence complicating congenital heart disease are prone to the development of sleep-disordered breathing as assessed by overnight oximetry. Further study into the prevalence and mechanisms of sleep-disordered breathing in a larger cohort are warranted. © 2016 Wiley Periodicals, Inc.

Peptidomics Analysis of Transient Regeneration in the Neonatal Mouse Heart.

PubMed

Fan, Yi; Zhang, Qijun; Li, Hua; Cheng, Zijie; Li, Xing; Chen, Yumei; Shen, Yahui; Wang, Liansheng; Song, Guixian; Qian, Lingmei

2017-09-01

Neonatal mouse hearts have completely regenerative capability after birth, but the ability to regenerate rapidly lost after 7 days, the mechanism has not been clarified. Previous studies have shown that mRNA profile of adult mouse changed greatly compared to neonatal mouse. So far, there is no research of peptidomics related to heart regeneration. In order to explore the changes of proteins, enzymes, and peptides related to the transient regeneration, we used comparative petidomics technique to compare the endogenous peptides in the mouse heart of postnatal 1 and 7 days. In final, we identified 236 differentially expressed peptides, 169 of which were upregulated and 67 were downregulated in the postnatal 1 day heart, and also predicted 36 functional peptides associated with transient regeneration. The predicted 36 candidate peptides are located in the important domains of precursor proteins and/or contain the post-transcriptional modification (PTM) sites, which are involved in the biological processes of cardiac development, cardiac muscle disease, cell proliferation, necrosis, and apoptosis. In conclusion, for the first time, we compared the peptidomics profiles of neonatal heart between postnatal 1 day and postnatal 7 day. This study provides a new direction and an important basis for the mechanism research of transient regeneration in neonatal heart. J. Cell. Biochem. 118: 2828-2840, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Description and initial evaluation of an educational and psychosocial support model for adults with congenitally malformed hearts.

PubMed

Rönning, Helén; Nielsen, Niels Erik; Swahn, Eva; Strömberg, Anna

2011-05-01

Various programmes for adults with congenitally malformed hearts have been developed, but detailed descriptions of content, rationale and goals are often missing. The aim of this study was to describe and make an initial evaluation of a follow-up model for adults with congenitally malformed hearts, focusing on education and psychosocial support by a multidisciplinary team (EPS). The model is described in steps and evaluated with regards to perceptions of knowledge, anxiety and satisfaction. The EPS model included a policlinic visit to the physician/nurse (medical consultation, computer-based and individual education face-to-face as well as psychosocial support) and a 1-month telephone follow-up. Fifty-five adults (mean age 34, 29 women) with the nine most common forms of congenitally malformed hearts participated in the EPS model as well as the 3-months follow-up. Knowledge about congenital heart malformation had increased in 40% of the participants at the 3-months follow-up. This study describes and evaluates a model that combines a multidisciplinary approach and computer-based education for follow-up of adults with congenitally malformed hearts. The EPS model was found to increase self-estimated knowledge, but further evaluations need to be conducted to prove patient-centred outcomes over time. The model is now ready to be implemented in adults with congenitally malformed hearts. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Immunostaining of dissected zebrafish embryonic heart.

PubMed

Yang, Jingchun; Xu, Xiaolei

2012-01-10

Zebrafish embryo becomes a popular in vivo vertebrate model for studying cardiac development and human heart diseases due to its advantageous embryology and genetics. About 100-200 embryos are readily available every week from a single pair of adult fish. The transparent embryos that develop ex utero make them ideal for assessing cardiac defects. The expression of any gene can be manipulated via morpholino technology or RNA injection. Moreover, forward genetic screens have already generated a list of mutants that affect different perspectives of cardiogenesis. Whole mount immunostaining is an important technique in this animal model to reveal the expression pattern of the targeted protein to a particular tissue. However, high resolution images that can reveal cellular or subcellular structures have been difficult, mainly due to the physical location of the heart and the poor penetration of the antibodies. Here, we present a method to address these bottlenecks by dissecting heart first and then conducting the staining process on the surface of a microscope slide. To prevent the loss of small heart samples and to facilitate solution handling, we restricted the heart samples within a circle on the surface of the microscope slides drawn by an immEdge pen. After the staining, the fluorescence signals can be directly observed by a compound microscope. Our new method significantly improves the penetration for antibodies, since a heart from an embryonic fish only consists of few cell layers. High quality images from intact hearts can be obtained within a much reduced procession time for zebrafish embryos aged from day 2 to day 6. Our method can be potentially extended to stain other organs dissected from either zebrafish or other small animals. Copyright © 2012 Journal of Visualized Experiments

[Genetics of congenital heart diseases].

PubMed

Bonnet, Damien

2017-06-01

Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Choline Diet and Its Gut Microbe-Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload-Induced Heart Failure.

PubMed

Organ, Chelsea L; Otsuka, Hiroyuki; Bhushan, Shashi; Wang, Zeneng; Bradley, Jessica; Trivedi, Rishi; Polhemus, David J; Tang, W H Wilson; Wu, Yuping; Hazen, Stanley L; Lefer, David J

2016-01-01

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients, is both elevated in the circulation of patients having heart failure and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerates atherosclerotic lesion development in ApoE-deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the low-density lipoprotein receptor knockout mouse. C57BL6/J mice were fed either a control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) starting 3 weeks before surgical transverse aortic constriction. Mice were studied for 12 weeks after transverse aortic constriction. Cardiac function and left ventricular structure were monitored at 3-week intervals using echocardiography. Twelve weeks post transverse aortic constriction, myocardial tissues were collected to evaluate cardiac and vascular fibrosis, and blood samples were evaluated for cardiac brain natriuretic peptide, choline, and TMAO levels. Pulmonary edema, cardiac enlargement, and left ventricular ejection fraction were significantly (P<0.05, each) worse in mice fed either TMAO- or choline-supplemented diets when compared with the control diet. In addition, myocardial fibrosis was also significantly greater (P<0.01, each) in the TMAO and choline groups relative to controls. Heart failure severity is significantly enhanced in mice fed diets supplemented with either choline or the gut microbe-dependent metabolite TMAO. The present results suggest that additional studies are warranted examining whether gut microbiota and the dietary choline → TMAO pathway contribute to increased heart failure susceptibility. © 2015 American Heart Association, Inc.

Engineering an in vitro organotypic model for studying cardiac hypertrophy.

PubMed

Jain, Aditi; Hasan, Jafar; Desingu, Perumal Arumugam; Sundaresan, Nagalingam R; Chatterjee, Kaushik

2018-05-01

Neonatal cardiomyocytes cultured on flat surfaces are commonly used as a model to study cardiac failure of diverse origin. A major drawback of such a system is that the cardiomyocytes do not exhibit alignment, organization and calcium transients, similar to the native heart. Therefore, there is a need to develop in vitro platforms that recapitulate the cellular microenvironment of the murine heart as organotypic models to study cardiovascular diseases. In this study, we report an engineered platform that mimics cardiac cell organization and function of the heart. For this purpose, microscale ridges were fabricated on silicon using ultraviolet lithography and reactive ion etching techniques. Physical characterization of the microstructures was done using scanning electron microscopy and atomic force microscopy. Cardiomyocytes grown on these micro-ridges showed global parallel alignment and elliptical nuclear morphology as observed in the heart. Interestingly, calcium currents traversed the engineered cardiomyocytes in a coordinated and directional manner. Moreover, the cardiomyocytes on the engineered substrates were found to be responsive to hypertrophic stimuli, as observed by the expression of a fetal gene, atrial natriuretic peptide and increase in calcium transients upon agonist treatment. Taken together, our work demonstrates that micro-ridges can be used to obtain cardiomyocyte response in vitro, which closely resembles mammalian heart. Copyright © 2018 Elsevier B.V. All rights reserved.

The Syncardia™ total artificial heart: in vivo, in vitro, and computational modeling studies

PubMed Central

Slepian, Marvin J.; Alemu, Yared; Soares, João Silva; Smith, Richard G.; Einav, Shmuel; Bluestein, Danny

2014-01-01

The SynCardia™ total artificial heart (TAH) is the only FDA-approved TAH in the world. The SynCardia™ TAH is a pneumatically driven, pulsatile system capable of flows of >9 L/min. The TAH is indicated for use as a bridge to transplantation (BTT) in patients at imminent risk of death from non-reversible bi-ventricular failure. In the Pivotal US approval trial the TAH achieved a BTT rate of >79%. Recently a multi-center, post-market approval study similarly demonstrated a comparable BTT rate. A major milestone was recently achieved for the TAH, with over 1100 TAHs having been implanted to date, with the bulk of implantation occurring at an ever increasing rate in the past few years. The TAH is most commonly utilized to save the lives of patients dying from end-stage bi-ventricular heart failure associated with ischemic or non-ischemic dilated cardiomyopathy. Beyond progressive chronic heart failure, the TAH has demonstrated great efficacy in supporting patients with acute irreversible heart failure associated with massive acute myocardial infarction. In recent years several diverse clinical scenarios have also proven to be well served by the TAH including severe heart failure associated with advanced congenital heart disease. failed or burned-out transplants, infiltrative and restrictive cardiomyopathies and failed ventricular assist devices. Looking to the future a major unmet need remains in providing total heart support for children and small adults. As such, the present TAH design must be scaled to fit the smaller patient, while providing equivalent, if not superior flow characteristics, shear profiles and overall device thrombogenicity. To aid in the development of a new “pediatric,” TAH an engineering methodology known as “Device Thrombogenicity Emulation (DTE)”, that we have recently developed and described, is being employed. Recently, to further our engineering understanding of the TAH, as steps towards next generation designs we have: (1) assessed of the degree of platelet reactivity induced by the present clinical 70 cc TAH using a closed loop platelet activity state assay, (2) modeled the motion of the TAH pulsatile mobile diaphragm, and (3) performed fluid-structure interactions and assessment of the flow behavior through inflow and outflow regions of the TAH fitted with modern bi-leaflet heart valves. Developing a range of TAH devices will afford biventricular replacement therapy to a wide range of patients, for both short and long-term therapy. PMID:23305813

[The Lived Experience of Patients with Heart Transplantation: A Phenomenological Study].

PubMed

Hwang, Younghui; Yi, Myungsun

2017-02-01

The purpose of this study was to describe the lived experience of patients with heart transplantation in Korea. Individual indepth interviews and a focus group interview were used to collect the data from nine patients who had heart transplantations in 2015. All interviews were audio-taped and verbatim transcripts were made for the analysis. Data were analyzed using Colaizzi's phenomenological method. Among the nine participants, eight were men. Mean age was 57.30 years. Six theme clusters emerged from the analysis. 'Joy of rebirth obtained by good luck' describes the pleasure and expectation of new life after narrow survival. 'Suffering from adverse drug effects' illustrates various psychosocial difficulties, such as low self-esteem, helplessness, alienation, and burnout, arising from the side effects of medications. 'Body and mind of being bewildered' illustrates disintegrated health and haunting fear of death. 'Alienation disconnected with society' describes isolated feeling of existence due to misunderstandings from society. 'Suffering overcome with gratitude and responsibility' includes overcoming experience through various social supports and suitable jobs. Finally, 'acceptance of suffering accompanied with new heart' illustrate changed perspective of life itself. The findings in this study provide deep understanding and insights of the lived experience of heart related illness for these patients and should help in the development of tailored-interventions for patients with heart transplantation. © 2017 Korean Society of Nursing Science

Improving prediction of heart transplantation outcome using deep learning techniques.

PubMed

Medved, Dennis; Ohlsson, Mattias; Höglund, Peter; Andersson, Bodil; Nugues, Pierre; Nilsson, Johan

2018-02-26

The primary objective of this study is to compare the accuracy of two risk models, International Heart Transplantation Survival Algorithm (IHTSA), developed using deep learning technique, and Index for Mortality Prediction After Cardiac Transplantation (IMPACT), to predict survival after heart transplantation. Data from adult heart transplanted patients between January 1997 to December 2011 were collected from the UNOS registry. The study included 27,860 heart transplantations, corresponding to 27,705 patients. The study cohorts were divided into patients transplanted before 2009 (derivation cohort) and from 2009 (test cohort). The receiver operating characteristic (ROC) values, for the validation cohort, computed for one-year mortality, were 0.654 (95% CI: 0.629-0.679) for IHTSA and 0.608 (0.583-0.634) for the IMPACT model. The discrimination reached a C-index for long-term survival of 0.627 (0.608-0.646) for IHTSA, compared with 0.584 (0.564-0.605) for the IMPACT model. These figures correspond to an error reduction of 12% for ROC and 10% for C-index by using deep learning technique. The predicted one-year mortality rates for were 12% and 22% for IHTSA and IMPACT, respectively, versus an actual mortality rate of 10%. The IHTSA model showed superior discriminatory power to predict one-year mortality and survival over time after heart transplantation compared to the IMPACT model.

Effect of exercise on diastolic function in heart failure patients: a systematic review and meta-analysis.

PubMed

Pearson, M J; Mungovan, S F; Smart, N A

2017-03-01

Diastolic dysfunction contributes to the development and progression of heart failure. Conventional echocardiography and tissue Doppler imaging are widely utilised in clinical research providing a number of indices of diastolic function valuable in the diagnosis and prognosis of heart failure patients. The aim of this meta-analysis was to quantify the effect of exercise training on diastolic function in patients with heart failure. Exercise training studies that investigate different indices of diastolic function in patients with heart failure have reported that exercise training improves diastolic function in these patients. We sought to add to the current literature by quantifying, where possible, the effect of exercise training on diastolic function. We conducted database searches (PubMed, EBSCO, EMBASE, and Cochrane Trials Register to 31 July 2016) for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, diastolic function and diastolic dysfunction'. Data from six studies, with a total of 266 heart failure with reduced ejection fraction (HFrEF) participants, 144 in intervention groups and 122 in control groups, indicated a significant reduction in the ratio of early diastolic transmitral velocity (E) to early diastolic tissue velocity (E') (E/E' ratio) with exercise training, exercise vs. control mean difference (MD) of -2.85 (95% CI -3.66 to -2.04, p < 0.00001). Data from five studies in heart failure with preserved ejection fraction (HFpEF) patients, with a total of 204 participants, 115 in intervention groups and 89 in control groups, also demonstrated a significant improvement in E/E' in exercise vs. control MD of -2.38 (95% CI -3.47 to -1.28, p < 0.0001).

Habitual chocolate consumption and the risk of incident heart failure among healthy men and women.

PubMed

Kwok, C S; Loke, Y K; Welch, A A; Luben, R N; Lentjes, M A H; Boekholdt, S M; Pfister, R; Mamas, M A; Wareham, N J; Khaw, K-T; Myint, P K

2016-08-01

We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Subclinical hypothyroidism: A common finding in adult patients with cyanotic congenital heart disease.

PubMed

Bak, Peter; Hjortshøj, Cristel S; Gaede, Peter; Idorn, Lars; Søndergaard, Lars; Jensen, Annette S

2018-03-01

Cyanotic congenital heart disease is a systemic disease, with effects on multiple organ systems. A high prevalence of subclinical hypothyroidism (SCH) has been reported in a small cohort of cyanotic congenital heart disease patients. Subclinical hypothyroidism has been associated with various adverse cardiovascular effects, as well as an increased risk of progression to overt hypothyroidism. The aim of this study was to examine the prevalence of SCH in cyanotic congenital heart disease patients, consider possible etiologies, and evaluate thyroid function over time. First, 90 clinically stable cyanotic congenital heart disease patients were examined with blood samples (thyroid-stimulating hormone, C-reactive protein, hemoglobin, hematocrit, and N-terminal pro-brain-natriuretic peptide) in a cross-sectional descriptive study. Second, a longitudinal follow-up study of 43 patients originating from the first study part, was carried out. These patients had thyroid function parameters (thyroid-stimulating hormone, thyroid hormones, and thyroid peroxidase antibodies) evaluated biannually. Elevated thyroid-stimulating hormone was present in 24% of the 90 screened patients. During follow-up (6.5 ± 1.0 years), SCH (defined as ≥2 consecutive elevated thyroid-stimulating hormone values) was present in 26%. Three patients progressed to overt hypothyroidism. Patients with SCH were younger (34 ± 12 vs 42 ± 16 years; P = .01) and had a lower oxygen saturation (80 ± 5 vs 84 ± 6%; P = .03). Subclinical hypothyroidism is a very common finding in cyanotic congenital heart disease. This is not associated with increased levels of C-reactive protein, heart failure, or autoimmunity but appears to be associated with cyanosis and age. Since the clinical impact of SCH is uncertain, further studies are needed to determine this. Regular thyroid evaluation is recommended in cyanotic congenital heart disease patients since SCH can develop to overt hypothyroidism. © 2017 Wiley Periodicals, Inc.

[Risk factors for ischemic heart disease in Mexico: a case control study].

PubMed

Camacho-Hernández, R; Corona-Muñiz, I; Vázquez-Martínez, J L; Martínez-Rodríguez, F; Escobedo-de la Peña, J

1995-01-01

A case control study was developed in order to assess the strength of the association of modifiable risk factors and the occurrence of coronary heart disease in Mexicans. A total of 284 incident cases of acute myocardial infarction and 284 age and sex matched hospitalized controls were included in the study. Information was obtained in all subjects regarding socio-demographic variables, history of diabetes, hypertension, smoking, obesity and serum cholesterol. A conditional logistic regression model, showed that diabetes mellitus, hypertension, smoking, hypercholesterolemia and obesity, explained the occurrence of coronary heart disease in the studied population. The risk of an acute myocardial infarction heavily increases in the extreme levels of exposure; and this risk is six fold higher in those who daily smoke more than 20 cigarettes, and it is eight fold higher in those subjects with a serum cholesterol greater than 240 mg/dl. Due to the increase in the occurrence of coronary heart disease in Mexico, and the strength of the association observed with these modifiable risk factors, a public health program to decrease its prevalence, is justified.

Knowledge and Oral Health Attitudes among Parents of Children with Congenital Heart Disease.

PubMed

Suvarna, Reshma; Rai, Kavita; Hegde, Amitha M

2011-01-01

Congenital heart disease (CHD) is a devastating complex of diseases resulting from defects of development. It affects more than 1 of every 100 live births. Early preventive dental care should be adjusted to the special needs of these children in their first years of life. Knowledge of parental attitudes and experiences of dental care are therefore important. Aim : This study was done to assess the knowledge and attitudes among parents of children with congenital heart disease towards oral health and dental care. Materials and methods : Parents (n = 105) of children with congenital heart disease of an age ranging from 0 to 16 years were included in the study. A questionnaire was used to assess the knowledge and oral health attitudes. Results : The parents' knowledge was fair but the oral health attitudes were not very satisfactory. The parents in this study also recognized the importance of oral health for the well-being of rest of the body. Conclusion : The results of this study indicate that parents' and children's attitudes toward oral health and dental care need to be improved.

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.

Changes in force and calcium sensitivity in the developing avian heart.

PubMed

Godt, R E; Fogaça, R T; Nosek, T M

1991-11-01

The aim of this study was to characterize the development of the contractile properties of intact and chemically skinned muscle from chicken heart and to compare these characteristics with those of developing mammalian heart reported by others. Small trabeculae were dissected from left ventricles of Arbor Acre chickens between embryonic day 7 and young adulthood (7 weeks post-hatching). At all ages, increasing extracellular calcium (0.45-3.6 mM) progressively increased twitch force of electrically stimulated trabeculae. Twitch force at 1.8 mM extracellular calcium, normalized to cross-sectional area, increased to a maximum at 1 day post-hatching, remained constant through 3 weeks post-hatching, but then decreased at 7 weeks post-hatching. The maximal calcium-activated force of trabeculae chemically skinned with Triton X-100 detergent increased to a maximum 2 days before the time of hatching and was not significantly changed up to 7 weeks post-hatching. Over the ages studied, average twitch force in 1.8 mM calcium was between 26 and 66% of maximal calcium-activated force after skinning, suggesting that the contractile apparatus is not fully activated during the twitch in normal Ringer. In skinned trabeculae, the calcium sensitivity of the contractile apparatus was higher in the embryo than in the young adult. These age-dependent changes in calcium sensitivity are correlated with isoform switching in troponin T. A decrease in pH from 7.0 to 6.5 decreased the calcium sensitivity of the contractile apparatus to a greater degree in skinned trabeculae from young adult hearts than in those from embryonic hearts. This change in susceptibility to acidosis is temporally associated with isoform switching in troponin I.(ABSTRACT TRUNCATED AT 250 WORDS)

Long Noncoding RNAs and Cardiac Disease.

PubMed

Greco, Simona; Salgado Somoza, Antonio; Devaux, Yvan; Martelli, Fabio

2017-08-30

To maintain homeostasis, gene expression has to be tightly regulated by complex and multiple mechanisms occurring at the epigenetic, transcriptional, and post-transcriptional levels. One crucial regulatory component is represented by long noncoding RNAs (lncRNAs), nonprotein-coding RNA species implicated in all of these levels. Thus, lncRNAs have been associated with any given process or pathway of interest in a variety of systems, including the heart. Recent Advances: Mounting evidence implicates lncRNAs in cardiovascular diseases (CVD) and progression and their presence in the blood of heart disease patients indicates that they are attractive potential biomarkers. Our understanding of the regulation and molecular mechanisms of action of most lncRNAs remains rudimentary. A challenge is represented by their often low evolutionary sequence conservation that limits the use of animal models for preclinical studies. Nevertheless, a growing number of lncRNAs with an impact on heart function is rapidly accumulating. In this study, we will discuss (a) lncRNAs that control heart homeostasis and disease; (b) concepts, approaches, and methodologies necessary to study lncRNAs in the heart; and (c) challenges posed and opportunities presented by lncRNAs as potential therapeutic targets and biomarkers. A deeper knowledge of the molecular mechanisms underpinning CVDs is necessary to develop more effective treatments. Further studies are needed to clarify the regulation and function of lncRNAs in the heart before they can be considered as therapeutic targets and disease biomarkers. Antioxid. Redox Signal. 00, 000-000.

A Percutaneously Implantable Fetal Pacemaker

PubMed Central

Zhou, Li; Vest, Adriana N.; Chmait, Ramen H.; Bar-Cohen, Yaniv; Pruetz, Jay; Silka, Michael; Zheng, Kaihui; Peck, Ray; Loeb, Gerald E.

2015-01-01

A miniaturized, self-contained pacemaker that could be implanted with a minimally invasive technique would dramatically improve the survival rate for fetuses that develop hydrops fetalis as a result of congenital heart block. We are currently validating a device that we developed to address this bradyarrhythmia. Preclinical studies in a fetal sheep model are underway to demonstrate that the device can be implanted via a minimally invasive approach, can mechanically withstand the harsh bodily environment, can induce effective contractions of the heart muscle with an adequate safety factor, and can successfully operate for the required device lifetime of three months using the previously-developed closed loop transcutaneous recharging system. PMID:25570982

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.

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.

Imaging the developing heart: synchronized time-lapse microscopy during developmental changes

NASA Astrophysics Data System (ADS)

Nelson, Carl J.; Buckley, Charlotte; Mullins, John J.; Denvir, Martin A.; Taylor, Jonathan

2018-02-01

How do you use imaging to analyse the development of the heart, which not only changes shape but also undergoes constant, high-speed, quasi-periodic changes? We have integrated ideas from prospective and retrospective optical gating to capture long-term, phase-locked developmental time-lapse videos. In this paper we demonstrate the success of this approach over a key developmental time period: heart looping, where large changes in heart shape prevent previous prospective gating approaches from capturing phase- locked videos. We use the comparison with other approaches to in vivo heart imaging to highlight the importance of collecting the most appropriate data for the biological question.

Parenting Behaviors, Parent Heart Rate Variability, and Their Associations with Adolescent Heart Rate Variability.

PubMed

Graham, Rebecca A; Scott, Brandon G; Weems, Carl F

2017-05-01

Adolescence is a potentially important time in the development of emotion regulation and parenting behaviors may play a role. We examined associations among parenting behaviors, parent resting heart rate variability, adolescent resting heart rate variability and parenting behaviors as moderators of the association between parent and adolescent resting heart rate variability. Ninety-seven youth (11-17 years; 49.5 % female; 34 % African American, 37.1 % Euro-American, 22.6 % other/mixed ethnic background, and 7.2 % Hispanic) and their parents (n = 81) completed a physiological assessment and questionnaires assessing parenting behaviors. Inconsistent discipline and corporal punishment were negatively associated with adolescent resting heart rate variability, while positive parenting and parental involvement were positively associated. Inconsistent discipline and parental involvement moderated the relationship between parent and adolescent resting heart rate variability. The findings provide evidence for a role of parenting behaviors in shaping the development of adolescent resting heart rate variability with inconsistent discipline and parental involvement potentially influencing the entrainment of resting heart rate variability in parents and their children.

Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis.

PubMed

Wu, Yanqing; Reece, E Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R; Yang, Peixin

2016-09-01

Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects remain largely unknown. We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus-induced congenital heart defects. A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin protein; endoplasmic reticulum chaperone gene expression; and XBP1 messenger RNA splicing, as well as increased cleaved caspase 3 and 8 in embryonic hearts. Furthermore, maternal type 2 diabetes mellitus triggered excessive apoptosis in ventricular myocardium, endocardial cushion, and outflow tract of the embryonic heart. Similar to those observations in type 1 diabetic embryopathy, maternal type 2 diabetes mellitus causes heart defects in the developing embryo manifested with oxidative stress, endoplasmic reticulum stress, and excessive apoptosis in heart cells. Copyright © 2016 Elsevier Inc. All rights reserved.

a New Approach to Physiologic Triggering in Medical Imaging Using Multiple Heart Sounds Alone.

NASA Astrophysics Data System (ADS)

Groch, Mark Walter

A new method for physiological synchronization of medical image acquisition using both the first and second heart sound has been developed. Heart sounds gating (HSG) circuitry has been developed which identifies, individually, both the first (S1) and second (S2) heart sounds from their timing relationship alone, and provides two synchronization points during the cardiac cycle. Identification of first and second heart sounds from their timing relationship alone and application to medical imaging has, heretofore, not been performed in radiology or nuclear medicine. The heart sounds are obtained as conditioned analog signals from a piezoelectric transducer microphone placed on the patient's chest. The timing relationships between the S1 to S2 pulses and the S2 to S1 pulses are determined using a logic scheme capable of distinguishing the S1 and S2 pulses from the heart sounds themselves, using their timing relationships, and the assumption that initially the S1-S2 interval will be shorter than the S2-S1 interval. Digital logic circuitry is utilized to continually track the timing intervals and extend the S1/S2 identification to heart rates up to 200 beats per minute (where the S1-S2 interval is not shorter than the S2-S1 interval). Clinically, first heart sound gating may be performed to assess the systolic ejection portion of the cardiac cycle, with S2 gating utilized for reproduction of the diastolic filling portion of the cycle. One application of HSG used for physiologic synchronization is in multigated blood pool (MGBP) imaging in nuclear medicine. Heart sounds gating has been applied to twenty patients who underwent analysis of ventricular function in Nuclear Medicine, and compared to conventional ECG gated MGBP. Left ventricular ejection fractions calculated from MGBP studies using a S1 and a S2 heart sound trigger correlated well with conventional ECG gated acquisitions in patients adequately gated by HSG and ECG. Heart sounds gating provided superior definition of the diastolic filling phase of the cardiac cycle by qualitative assessment of the left ventricular volume time -activity curves. Heart sounds physiological synchronization has potential to be used in other imaging modalities, such as magnetic resonance imaging, where the ECG is distorted due to the electromagnetic environment within the imager.

Factors influencing self-care behaviors of African Americans with heart failure: a photovoice project.

PubMed

Woda, Aimee; Belknap, Ruth Ann; Haglund, Kristin; Sebern, Margaret; Lawrence, Ashley

2015-01-01

The purpose of this study was to understand the influences of heart failure (HF) self-care among low income, African Americans. Compared to all other racial groups, African Americans have the highest risk of developing HF, coupled with high mortality and morbidity rates. Using the photovoice method, participants related important lifestyle factors through photography. The participants and researcher met for reflection and discussion 2 h per week for six weeks. Four themes emerged: family support gives me the push I need, social interaction lifts me up, improving my mind to lift depression can improve my heart, and it is important but challenging to follow the HF diet. The findings from this study may assist policy makers, health care professionals, patients, and support systems in understanding the complexity of engaging in HF self-care. This understanding may lead to the development of appropriate patient-centered assessments and interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of ethanol vapour exposure on atrial and ventricular walls of chick embryos.

PubMed

Kamran, Kiran; Khan, Muhammad Yunus; Minhas, Liaqat Ali

2016-10-01

To study the effects of ethanol vapour exposure on atrial and ventricular walls of heart in chick embryo. The study design was experimental, conducted at Islamabad Centre of College of Physicians and Surgeons, Pakistan. One hundred and eighty chicken eggs were divided into two groups, experimental and control, of 90 eggs each. Each group was subdivided into three subgroups of 30 eggs each based on the day of sacrifice. Experimental group was exposed to ethanol vapours and then compared with age matched controls. The thickness of atrial and ventricular walls along with lengths of valvular cusps increased in hearts of day 7 and day 10 chick embryos in experimental group. There was thinning of walls and decreased length of valvular cusps in hearts of experimental chicks on hatching as compared to age matched controls. Ethanol vapour exposure during development causes cardiac and septal wall thickening during initial days of development followed by cardiac and septal wall thinning which is a classical picture of alcohol induced cardiomyopathies.

Redox Signaling in the Right Ventricle.

PubMed

Suzuki, Yuichiro J; Shults, Nataliia V

2017-01-01

Pulmonary hypertension is a devastating disease without cure. The major cause of death among patients with pulmonary hypertension is right heart failure; however, biology of the right heart is not well understood. This lack of knowledge interferes with developing effective therapeutic strategies to treat these patients. In this chapter, we summarize studies performed in our laboratory that investigated the role of redox signaling in the regulation of the right ventricle (RV), using rat models of experimental pulmonary hypertension and right heart failure. Specifically, this chapter covers the topics of (a) redox regulation of serotonin signaling in the RV, (b) the carbonylation-degradation pathway of signal transduction in RV hypertrophy and (c) oxidative modifications in the RV of the SU5416/ovalbumin model of pulmonary arterial hypertension. These studies revealed that redox regulation in the RV is complex and simply giving lots of antioxidants to patients will unlikely benefit them. Deeper understanding of specific and selective redox mechanisms should shed light on how we can develop therapeutic strategies by modulating redox reactions.

Complete inhibition of creatine kinase in isolated perfused rat hearts

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

Fossel, E.T.; Hoefeler, H.

1987-01-01

Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts aremore » able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.« less

Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

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

Montaigne, David; Marechal, Xavier; Baccouch, Riadh

2010-05-01

The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solutionmore » containing 1 muM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt{sub max} of 105 +- 8 mN/s in control hearts vs. 49 +- 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 +- 0.2 in control hearts vs. 2.2 +- 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 +- 1 muM cytochrome c/min/mg in control hearts vs. 14 +- 3 muM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.« less

The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo.

PubMed

Rajendran, Saranya; Sundaresan, Lakshmikirupa; Rajendran, Krithika; Selvaraj, Monica; Gupta, Ravi; Chatterjee, Suvro

2016-02-11

Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel in vivo model to study the flow experienced by developing endothelium. Using this model, we aimed to capture the transcriptome dynamics of the pre- and post-flow conditions. RNA was isolated from extra embryonic area vasculosa (EE-AV) pooled from three chick embryos between HH10-HH13 and RNA sequencing was performed. The whole transcriptome sequencing of chick identified up-regulation of some of the previously well-known mechanosensitive genes including NFR2, HAND1, CTGF and KDR. GO analyses of the up-regulated genes revealed enrichment of several biological processes including heart development, extracellular matrix organization, cell-matrix adhesion, cell migration, blood vessel development, patterning of blood vessels, collagen fibril organization. Genes encoding for gap junctions proteins which are involved in vascular remodeling and arterial-venous differentiation, and genes involved in cell-cell adhesion, and ECM interactions were significantly up-regulated. Validation of selected genes through semi quantitative PCR was performed. The study indicates that shear stress plays a major role in development. Through appropriate validation, this platform can serve as an in vivo model to study conditions of disturbed flow in pathology as well as normal flow during development.

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.

The effects of heart failure on renal function.

PubMed

Udani, Suneel M; Koyner, Jay L

2010-08-01

Heart-kidney interactions have been increasingly recognized by clinicians and researchers who study and treat heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of concomitant cardiac and renal dysfunction remains unclear; however, evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. 2010 Elsevier Inc. All rights reserved.

The Effects of Heart Failure on Renal Function

PubMed Central

Udani, Suneel M; Koyner, Jay L

2010-01-01

Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

Engineered Microenvironments for the Maturation and Observation of Human Embryonic Stem Cell Derived Cardiomyocytes

NASA Astrophysics Data System (ADS)

Salick, Max R.

The human heart is a dynamic system that undergoes substantial changes as it develops and adapts to the body's growing needs. To better understand the physiology of the heart, researchers have begun to produce immature heart muscle cells, or cardiomyocytes, from pluripotent stem cell sources with remarkable efficiency. These stem cell-derived cardiomyocytes hold great potential in the understanding and treatment of heart disease; however, even after prolonged culture, these cells continue to exhibit an immature phenotype, as indicated by poor sarcomere organization and calcium handling, among other features. The lack of maturation that is observed in these cardiomyocytes greatly limits their applicability towards drug screening, disease modeling, and cell therapy applications. The mechanical environment surrounding a cell has been repeatedly shown to have a large impact on that cell's behavior. For this reason, we have implemented micropatterning methods to mimic the level of alignment that occurs in the heart in vivo in order to study how this alignment may help the cells to produce a more mature sarcomere phenotype. It was discovered that the level of sarcomere organization of a cardiomyocyte can be strongly influenced by the micropattern lane geometry on which it adheres. Steps were taken to optimize this micropattern platform, and studies of protein organization, gene expression, and myofibrillogenesis were conducted. Additionally, a set of programs was developed to provide quantitative analysis of the level of sarcomere organization, as well as to assist with several other tissue engineering applications.

[Assessment of medical management of heart failure at National Hospital Blaise COMPAORE].

PubMed

Kambiré, Y; Konaté, L; Diallo, I; Millogo, G R C; Kologo, K J; Tougouma, J B; Samadoulougou, A K; Zabsonré, P

2018-05-09

The aim of this study was to assess the quality of medical management of heart failure at the National Hospital Blaise Compaoré according to the international guidelines. A retrospective study was performed including consecutive patients admitted for heart failure documented sonographically from October 2012 to March 2015 in the Medicine and Medical Specialties Department of National Hospital Blaise Compaore with a minimum follow-up of six weeks. Data analysis was made by the SPSS 20.0 software. Eighty-four patients, mean age of 57.61±18.24 years, were included. It was an acute heart failure in 84.5% of patients with systolic left ventricular function impaired (77.4%). The rate of prescription of different drugs in heart failure any type was 88.1% for loop diuretics; 77.1% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and 65.5% for betablockers. In patients with systolic dysfunction, 84.62% of patients were received the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and 75.38% for betablockers. Exercise rehabilitation was undergoing in 10.7% of patients. The death rate was 16.7% and hospital readmission rate of 16.7%. The prescription rate of major heart failure drugs is satisfactory. Cardiac rehabilitation should be developed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Modalities and future prospects of gene therapy in heart transplantation.

PubMed

Vassalli, Giuseppe; Roehrich, Marc-Estienne; Vogt, Pierre; Pedrazzini, Giovanni B; Siclari, Francesco; Moccetti, Tiziano; von Segesser, Ludwig K

2009-06-01

Heart transplantation is the treatment of choice for many patients with end-stage heart failure. Its success, however, is limited by organ shortage, side effects of immunosuppressive drugs, and chronic rejection. Gene therapy is conceptually appealing for applications in transplantation, as the donor organ is genetically manipulated ex vivo before transplantation. Localised expression of immunomodulatory genes aims to create a state of immune privilege within the graft, which could eliminate the need for systemic immunosuppression. In this review, recent advances in the development of gene therapy in heart transplantation are discussed. Studies in animal models have demonstrated that genetic modification of the donor heart with immunomodulatory genes attenuates ischaemia-reperfusion injury and rejection. Alternatively, bone marrow-derived cells genetically engineered with donor-type major histocompatibility complex (MHC) class I or II promote donor-specific hyporesponsiveness. Genetic engineering of naïve T cells or dendritic cells may induce regulatory T cells and regulatory dendritic cells. Despite encouraging results in animal models, however, clinical gene therapy trials in heart transplantation have not yet been started. The best vector and gene to be delivered remain to be identified. Pre-clinical studies in non-human primates are needed. Nonetheless, the potential of gene therapy as an adjunct therapy in transplantation is essentially intact.