Andalusian registry of heart transplantation: first official adult heart transplant report 2010.

PubMed

Arizón, J M; Lage, E; Castillo, J C; López-Granados, A; Sobrino, M; Segura, C; Menjibar, V

2012-09-01

This is the first official report of the Andalusian Registry of Heart Transplantation. Since 1986, two centers in the community have been authorized to perform adult heart transplantation. Until 2010, 854 adult heart transplantation procedures were performed, which constitute the basis of the present report. Clinical features and survival are analyzed. The leading reason for heart transplantation was ischemic cardiomyopathy (34%) and nonischemic dilated cardiomyopathy (34%). The mean age of the recipients was 46 ± 16 years and the mean age of the donors was 29 ± 13 years. After a median follow-up of 106 months, the mean survival was 13.4 ± 0.6 years. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-05-01

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

Resonance of about-weekly human heart rate rhythm with solar activity change.

PubMed

Cornelissen, G; Halberg, F; Wendt, H W; Bingham, C; Sothern, R B; Haus, E; Kleitman, E; Kleitman, N; Revilla, M A; Revilla, M; Breus, T K; Pimenov, K; Grigoriev, A E; Mitish, M D; Yatsyk, G V; Syutkina, E V

1996-12-01

In several human adults, certain solar activity rhythms may influence an about 7-day rhythm in heart rate. When no about-weekly feature was found in the rate of change in sunspot area, a measure of solar activity, the double amplitude of a circadian heart rate rhythm, approximated by the fit of a 7-day cosine curve, was lower, as was heart rate corresponds to about-weekly features in solar activity and/or relates to a sunspot cycle.

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

PubMed

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

2017-06-01

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

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

Oxygen consumption of human heart cells in monolayer culture.

PubMed

Sekine, Kaori; Kagawa, Yuki; Maeyama, Erina; Ota, Hiroki; Haraguchi, Yuji; Matsuura, Katsuhisa; Shimizu, Tatsuya

2014-09-26

Tissue engineering in cardiovascular regenerative therapy requires the development of an efficient oxygen supply system for cell cultures. However, there are few studies which have examined human cardiomyocytes in terms of oxygen consumption and metabolism in culture. We developed an oxygen measurement system equipped with an oxygen microelectrode sensor and estimated the oxygen consumption rates (OCRs) by using the oxygen concentration profiles in culture medium. The heart is largely made up of cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells. Therefore, we measured the oxygen consumption of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), cardiac fibroblasts, human cardiac microvascular endothelial cell and aortic smooth muscle cells. Then we made correlations with their metabolisms. In hiPSC-CMs, the value of the OCR was 0.71±0.38pmol/h/cell, whereas the glucose consumption rate and lactate production rate were 0.77±0.32pmol/h/cell and 1.61±0.70pmol/h/cell, respectively. These values differed significantly from those of the other cells in human heart. The metabolism of the cells that constitute human heart showed the molar ratio of lactate production to glucose consumption (L/G ratio) that ranged between 1.97 and 2.2. Although the energy metabolism in adult heart in vivo is reported to be aerobic, our data demonstrated a dominance of anaerobic glycolysis in an in vitro environment. With our measuring system, we clearly showed the differences in the metabolism of cells between in vivo and in vitro monolayer culture. Our results regarding cell OCRs and metabolism may be useful for future tissue engineering of human heart. Copyright © 2014 Elsevier Inc. All rights reserved.

Localisation of atrial natriuretic peptide immunoreactivity in the ventricular myocardium and conduction system of the human fetal and adult heart.

PubMed Central

Wharton, J; Anderson, R H; Springall, D; Power, R F; Rose, M; Smith, A; Espejo, R; Khaghani, A; Wallwork, J; Yacoub, M H

1988-01-01

Atrial natriuretic peptide immunoreactivity was found in ventricular and atrial tissues with specific antisera raised to the amino and carboxy terminal regions of the precursor molecule. In 13 developing human hearts (7-24 weeks' gestation) the immunoreactivity was concentrated in the atrial myocardium and ventricular conduction system but it was also detected in the early fetal ventricular myocardium. Immunoreactivity in five normal adults was largely confined to the atrial myocardium although it was also found in the ventricular conduction tissues of hearts removed from 10 patients who were undergoing cardiac transplantation. The ventricular conduction system is an extra-atrial site for the synthesis of atrial natriuretic peptide. In the failing heart this synthesis may be further supplemented by expression of the gene in the ventricular myocardium. It is possible that ventricular production of the peptide contributes to the raised circulating concentrations of atrial natriuretic peptide immunoreactivity found in severe congestive heart disease, particularly in patients with dilated cardiomyopathy. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:2973340

Human care system for heart-rate and human-movement trajectory in home and its application to detect mental disease

NASA Astrophysics Data System (ADS)

Hata, Yutaka; Kanazawa, Seigo; Endo, Maki; Tsuchiya, Naoki; Nakajima, Hiroshi

2012-06-01

This paper proposes a heart rate monitoring system for detecting autonomic nervous system by the heart rate variability using an air pressure sensor to diagnose mental disease. Moreover, we propose a human behavior monitoring system for detecting the human trajectory in home by an infrared camera. In day and night times, the human behavior monitoring system detects the human movement in home. The heart rate monitoring system detects the heart rate in bed in night time. The air pressure sensor consists of a rubber tube, cushion cover and pressure sensor, and it detects the heart rate by setting it to bed. It unconstraintly detects the RR-intervals; thereby the autonomic nervous system can be assessed. The autonomic nervous system analysis can examine the mental disease. While, the human behavior monitoring system obtains distance distribution image by an infrared camera. It classifies adult, child and the other object from distance distribution obtained by the camera, and records their trajectories. This behavior, i.e., trajectory in home, strongly corresponds to cognitive disorders. Thus, the total system can detect mental disease and cognitive disorders by uncontacted sensors to human body.

Adult Congenital Heart Disease: Scope of the Problem.

PubMed

Mazor Dray, Efrat; Marelli, Ariane J

2015-11-01

This article reviews the changing epidemiology of congenital heart disease summarizing its impact on the demographics of the congenital heart disease population and the progress made in order to improve outcomes in this patient population. Birth prevalence of congenital heart disease can be modified by many factors. As a result of decreasing mortality and increasing survival in all forms of congenital heart disease, the median age of patients has increased and adults now compose two-thirds of patients with congenital heart disease. Disease burden and resulting health services utilization increase significantly across the lifespan. Bridging the gap between policy and quality of care can be improved by referral to specialized adult congenital heart disease centers and planning delivery of specialized services that are commensurate with population needs, program accreditation criteria and certified training of designated workforce. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Telocytes and putative stem cells in ageing human heart

PubMed Central

Popescu, Laurentiu M; Curici, Antoanela; Wang, Enshi; Zhang, Hao; Hu, Shengshou; Gherghiceanu, Mihaela

2015-01-01

Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes (CMs). Anyway, the presence of telocytes (TCs) has been overlooked, since they were described in 2010 (visit http://www.telocytes.com). Also, the number of cardiac stem cells (CSCs) has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium (appendages). Three age-related groups were studied: newborns (17 days–1 year), children (6–17 years) and adults (34–60 years). Morphometry was performed on low-magnification electron microscope images using computer-assisted technology. We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm2) increased with several hundreds in children and adults versus newborns. CMs are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Images of CMs mitoses were seen in the 17-day newborns. Interestingly, no lipofuscin granules were found in CMs of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52–62%; vascular smooth muscle cells and pericytes 22–28%, Schwann cells with nerve endings 6–7%, fibroblasts 3–10%, macrophages 1–8%, TCs about 1% and stem cells less than 1%. We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, TCs represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports CSCs. The myocardial (very) low capability to regenerate may be explained by the number of CSCs, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults). PMID:25545142

Self-care in older adults with heart failure: an integrative review.

PubMed

Zavertnik, Jean Ellen

2014-01-01

The aims of this integrative review were to examine the evidence specific to self-care in older adults, 65 years or older, with heart failure and to indicate best nursing practice interventions for use in this population. Self-care is a complex set of activities involving self-care maintenance and self-care management. Age-related and psychosocial factors impact older patients' ability to engage effectively in self-care practices. Although self-care processes are the focus of the investigation, few studies provide implications specific for the older adult population. Limited research on heart failure self-care in the older adult meets the age criterion of 65 years or older. A comprehensive search of the literature was performed using Medline, CINAHL, and the Cochrane Library, as well as an ancestry approach of reference lists of selected studies. Eligible studies were randomized controlled trial, qualitative, quantitative, and mixed-method design studies on older adults with heart failure related to self-care for the years 2002-2012. Three themes of self-care were noted in the selected studies: patient-related factors, patient education, and telemonitoring. The patient-related factors identified were barriers to self-care such as age-related symptoms, cognitive factors, and social issues. The interventions promoting self-care were patient education (self-care knowledge) and telemonitoring (augmenting symptom recognition). Patient education tailored to older adults may be beneficial. Telemonitoring is an appropriate self-care enhancement tool for selected older adults. More emphasis needs to be placed on interventions to assist older adults with heart failure in symptom recognition and early notification of healthcare providers. As the population ages, a need for evidence-based care for older adults with heart failure is warranted. Heart failure self-care interventions do not address the special considerations of the older heart failure patient. To determine the

Drug Therapy in Adult Congenital Heart Disease.

PubMed

Contractor, Tahmeed; Levin, Vadim; Mandapati, Ravi

2017-06-01

Adults with congenital heart disease are at risk for atrial and ventricular arrhythmias that can lead to an increased morbidity as well as mortality. When catheter ablation is not an option or unsuccessful, antiarrhythmic drugs are the mainstay of treatment. There is limited data on the use of antiarrhythmics in this population. The purpose of this article is to discuss the practical aspects of the use of antiarrhythmics in adults with congenital heart disease. Several tables have been provided to provide clinicians a reference for daily use. Copyright © 2017 Elsevier Inc. All rights reserved.

Medical therapy in adults with congenital heart disease.

PubMed

Book, Wendy M; Shaddy, Robert E

2014-01-01

Heart failure is a common late complication in adults with congenital heart defects, both repaired and unrepaired. The onset of clinical heart failure is associated with increased morbidity and mortality. Some patients with congenital heart disease may benefit from medications shown to improve survival in the population with acquired heart failure, but these same therapies may be of no benefit to other patients. Further studies are needed to better guide the choice of medical therapies. Copyright © 2014 Elsevier Inc. All rights reserved.

Correlates of posttraumatic stress disorder in adults with congenital heart disease.

PubMed

Eslami, Bahareh

2017-05-01

The aims of this study were to compare the level of posttraumatic stress disorder between adults with and without congenital heart disease, and to examine the correlates of posttraumatic stress disorder (e.g., sociodemographics). Cross-sectional. Two university-affiliated heart hospitals in Tehran, Iran. A sample of 347 adults with congenital heart disease aged 18-64 years (52% women), and 353 adults without congenital heart disease matched by sex and age (±2 years) was recruited. The PTSD Scale: Self-report version was used to assess the diagnosis and severity of posttraumatic stress disorder. Hierarchical multivariate logistic regression analyses were performed to explore correlates of likely posttraumatic stress disorder diagnosis among each group of participants. The posttraumatic stress disorder in the patients was comparable to those of the control group, except for increased arousal (P = .027) which was scored higher among the patients. Over 52% of adults with congenital heart disease met the criteria for a likely posttraumatic stress disorder diagnosis compared with 48% of adults without congenital heart disease. The regression analyses among patients revealed that elevated depressive symptoms (OR = 1.27) and a positive history of cardiac surgery (OR = 2.02) were significantly associated with posttraumatic stress disorder. The model could explain 29% of the variance in posttraumatic stress disorder. The high and comparable prevalence of posttraumatic stress disorder among patients and nonpatients highlight the significance of the context in which adults with congenital heart disease may face other/additional stressors than disease-related ones, an issue that clinicians need also take into account. Furthermore, the association of posttraumatic stress disorder with elevated depressive symptoms warrant a comprehensive psychological assessment and management of adults with congenital heart disease, in particular among those with a history of

A review of the economics of adult congenital heart disease.

PubMed

Seckeler, Michael D; Thomas, Ian D; Andrews, Jennifer; Joiner, Keith; Klewer, Scott E

2016-01-01

Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.

Global transcriptional profiling reveals similarities and differences between human stem cell-derived cardiomyocyte clusters and heart tissue.

PubMed

Synnergren, Jane; Améen, Caroline; Jansson, Andreas; Sartipy, Peter

2012-02-27

It is now well documented that human embryonic stem cells (hESCs) can differentiate into functional cardiomyocytes. These cells constitute a promising source of material for use in drug development, toxicity testing, and regenerative medicine. To assess their utility as replacement or complement to existing models, extensive phenotypic characterization of the cells is required. In the present study, we used microarrays and analyzed the global transcription of hESC-derived cardiomyocyte clusters (CMCs) and determined similarities as well as differences compared with reference samples from fetal and adult heart tissue. In addition, we performed a focused analysis of the expression of cardiac ion channels and genes involved in the Ca(2+)-handling machinery, which in previous studies have been shown to be immature in stem cell-derived cardiomyocytes. Our results show that hESC-derived CMCs, on a global level, have a highly similar gene expression profile compared with human heart tissue, and their transcriptional phenotype was more similar to fetal than to adult heart. Despite the high similarity to heart tissue, a number of significantly differentially expressed genes were identified, providing some clues toward understanding the molecular difference between in vivo sourced tissue and stem cell derivatives generated in vitro. Interestingly, some of the cardiac-related ion channels and Ca(2+)-handling genes showed differential expression between the CMCs and heart tissues. These genes may represent candidates for future genetic engineering to create hESC-derived CMCs that better mimic the phenotype of the cardiomyocytes present in the adult human heart.

Increasing mortality burden among adults with complex congenital heart disease.

PubMed

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

2015-01-01

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

Energy demand of cardioplegically perfused human hearts.

PubMed

Preusse, C J; Winter, J; Schulte, H D; Bircks, W

1985-01-01

Human adult hearts with aortic valve disease (n = 20) and hypertrophic obstructive cardiomyopathy (n = 1) were perfused intraoperatively with cold histidine buffered Bretschneider solution. During a seven minute cardioplegic perfusion the temperature level, the electrolyte level, the resistance of the left (LCA) and right coronary artery (RCA), and myocardial O2 consumption were analysed. Equilibration of K+ was terminated shortly after the start of the perfusion while Na+ equilibration lasted for about 5 minutes. Resistance of RCA did not change significantly, but that of the LCA was diminished significantly (p less than 0.025) within the perfusion period indicating a delayed washout of calcium from the extracellular space. Myocardial O2 consumption was reduced from 2.71 ml/min (1. minute) to 1.51 ml/min (4. minute) to 0.93 ml/min (7. minute) although the temperature had reached a low level after 3 minutes. The difference between 4. to 7. minutes is significant (p less than 0.001). By our results it is concluded that in adult hearts high-volume cardioplegic perfusion at a flow rate of 1 ml/min X gm at a perfusion pressure of 40 to 50 mmHg should be performed for at least 6 to 7 minutes to achieve a sufficient intra-ischemic myocardial protection.

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.

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

PubMed

Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

2005-05-01

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

Adult Learners' Preferred Methods of Learning Preventative Heart Disease Care

ERIC Educational Resources Information Center

Alavi, Nasim

2016-01-01

The purpose of this study was to investigate the preferred method of learning about heart disease by adult learners. This research study also investigated if there was a statistically significant difference between race/ethnicity, age, and gender of adult learners and their preferred method of learning preventative heart disease care. This…

Overview of adult congenital heart transplants

PubMed Central

Morales, David

2018-01-01

Transplantation for adult patients with congenital heart disease (ACHD) is a growing clinical endeavor in the transplant community. Understanding the results and defining potential high-risk patient subsets will allow optimization of patient outcomes. This review summarizes the scope of ACHD transplantation, the mechanisms of late ventricular dysfunction, the ACHD population at risk of developing heart failure, the indications and potential contraindications for transplant, surgical considerations, and post-transplant outcomes. The findings reveal that 3.3% of adult heart transplants occur in ACHD patients. The potential mechanisms for the development of late ventricular dysfunction include a morphologic systemic right ventricle, altered coronary perfusion, and ventricular noncompaction. The indications for transplant in ACHD patients include systemic ventricular failure refractory medical therapy, Fontan patients failing from chronic passive pulmonary circulation, and progressive cyanosis leading to functional decline. Transplantation in ACHD patients can be quite complex and may require extensive reconstruction of the branch pulmonary arteries, systemic veins, or the aorta. Vasoplegia, bleeding, and graft right ventricular dysfunction can complicate the immediate post-transplant period. The post-transplant operative mortality ranges between 14% and 39%. The majority of early mortality occurs in ACHD patients with univentricular congenital heart disease. However, there has been improvement in operative survival in more contemporary studies. In conclusion, the experience with cardiac transplantation for ACHD patients with end-stage heart failure is growing, and high-risk patient subsets have been defined. Significant strides have been made in developing evidence-based guidelines of indications for transplant, and the intraoperative management of complex reconstruction has evolved. With proper patient selection, more aggressive use of mechanical circulatory support

"Young at heart": Regenerative potential linked to immature cardiac phenotypes.

PubMed

Gomes, Renata S M; Skroblin, Philipp; Munster, Alex B; Tomlins, Hannah; Langley, Sarah R; Zampetaki, Anna; Yin, Xiaoke; Wardle, Fiona C; Mayr, Manuel

2016-03-01

The adult human myocardium is incapable of regeneration; yet, the zebrafish (Danio rerio) can regenerate damaged myocardium. Similar to the zebrafish heart, hearts of neonatal, but not adult mice are capable of myocardial regeneration. We performed a proteomics analysis of adult zebrafish hearts and compared their protein expression profile to hearts from neonatal and adult mice. Using difference in-gel electrophoresis (DIGE), there was little overlap between the proteome from adult mouse (>8weeks old) and adult zebrafish (18months old) hearts. Similarly, there was a significant degree of mismatch between the protein expression in neonatal and adult mouse hearts. Enrichment analysis of the selected proteins revealed over-expression of DNA synthesis-related proteins in the cardiac proteome of the adult zebrafish heart similar to neonatal and 4days old mice, whereas in hearts of adult mice there was a mitochondria-related predominance in protein expression. Importantly, we noted pronounced differences in the myofilament composition: the adult zebrafish heart lacks many of the myofilament proteins of differentiated adult cardiomyocytes such as the ventricular isoforms of myosin light chains and nebulette. Instead, troponin I and myozenin 1 were expressed as skeletal isoforms rather than cardiac isoforms. The relative immaturity of the adult zebrafish heart was further supported by cardiac microRNA data. Our assessment of zebrafish and mammalian hearts challenges the assertions on the translational potential of cardiac regeneration in the zebrafish model. The immature myofilament composition of the fish heart may explain why adult mouse and human cardiomyocytes lack this endogenous repair mechanism. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Human heart by art.

PubMed

Tamir, Abraham

2012-11-01

Heart is of great importance in maintaining the life of the body. Enough to stop working for a few minutes to cause death, and hence the great importance in physiology, medicine, and research. This fact was already emphasized in the Bible in the Book of Proverbs, chapter 4 verse 23: "Keep your heart with all diligence, for out of it is the wellspring of life." Art was able to demonstrate the heart from various aspects; realistically, as done by Leonardo de Vinci who demonstrated the halves of the heart and its blood vessels. Symbolically, as a source of life, the heart was demonstrated by the artist Mrs. Erlondeiel, as a caricature by Salvador Dali, as an open heart by Sawaya, etc. Finally, it should be emphasized that different demonstrations of the human heart by many artworks make this most important organ of our body (that cannot be seen from outside) more familiar and clearer to us. And this is the purpose of this article-to demonstrate the heart through a large number of artworks of different kinds.

Outcomes after ABO-incompatible heart transplantation in adults: A registry study.

PubMed

Bergenfeldt, Henrik; Andersson, Bodil; Bućin, Dragan; Stehlik, Josef; Edwards, Leah; Rådegran, Göran; Nilsson, Johan

2015-07-01

In the past, ABO incompatibility was considered an absolute contraindication to heart transplantation (HT) in adults. Advances in ABO-incompatible HT in pediatric patients and ABO-incompatible abdominal transplantation in adult patients have led to clinical exploration of intentional ABO-incompatible HT in adults. However, it is not well known how outcomes in ABO-incompatible adult heart transplant recipients compare with outcomes in ABO-compatible recipients. We analyzed International Society for Heart and Lung Transplantation transplant registry data from heart donors and recipients ≥18 years old at the time of transplant for HT performed between 1988 and 2011. We compared baseline characteristics and post-transplant outcomes in ABO-incompatible and ABO-compatible HT. Death or retransplantation was the composite primary end-point. Among 76,663 adult patients undergoing HT between 1988 and June 30, 2011, 94 ABO-incompatible heart transplants were performed. The incidence of death or retransplantation in the ABO-incompatible group was higher than in the ABO-compatible group: 21% vs 9% at 30 days (hazard ratio = 2.38, p < 0.001) and 36% vs 19% at 1 year after transplant. However, ABO-incompatible grafts surviving past the first year after transplant had a similar incidence of failure compared with the ABO-compatible group. After 2005, the rate ABO-incompatible HT in adults increased, likely as a result of planned, intentional (rather than accidental) ABO-incompatible HT. In this group of patients, short-term and long-term incidence of death or retransplantation was similar to ABO-compatible recipients (p = 0.822): 7% at 30 days and 19% at 1 year after transplantation. We found no difference in incidence of death or retransplantation between ABO-compatible and ABO-incompatible HT in patients who underwent transplantation after 2005. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease.

PubMed

Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul

2016-04-01

Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

PubMed

Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D; van den Hoff, Maurice J B; Butte, Manish J; Yang, Phillip C; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

2015-09-24

The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

Congenital Heart Defects in Adults : A Field Guide for Cardiologists

PubMed Central

Romfh, Anitra; Pluchinotta, Francesca Romana; Porayette, Prashob; Valente, Anne Marie; Sanders, Stephen P.

2013-01-01

Advances in cardiology and cardiac surgery allow a large proportion of patients with congenital heart defects to survive into adulthood. These patients frequently develop complications characteristic of the defect or its treatment. Consequently, adult cardiologists participating in the care of these patients need a working knowledge of the more common defects. Occasionally, patients with congenital heart defects such as atrial septal defect, Ebstein anomaly or physiologically corrected transposition of the great arteries present for the first time in adulthood. More often patients previously treated in pediatric cardiology centers have transitioned to adult congenital heart disease centers for ongoing care. Some of the more important defects in this category are tetralogy of Fallot, transposition of the great arteries, functionally single ventricle defects, and coarctation. Through this field guide, we provide an overview of the anatomy of selected defects commonly seen in an adult congenital practice using pathology specimens and clinical imaging studies. In addition, we describe the physiology, clinical presentation to the adult cardiologist, possible complications, treatment options, and outcomes. PMID:24294540

The Role of Beta-Blocker in Heart Failure in Adults with Congenital Heart Disease.

PubMed

Norozi, Kambiz

2014-01-01

Thanks to the enormous progress in the field of cardiac surgery and paediatric cardiology since the mid of 20th century, more and more children with congenital heart defects reach the adulthood. This on the other hand encounter physician and patients various problems due to late complications after the heart surgery like congestive heart failure, arrhythmia and sudden death. One of the challenging area is the medical management of heart failure in these patients with complex anatomy and hemodynamics. The lack of evidence of the effectiveness of the anti congestive medications in this population in from of large randomized controlled trials, makes it difficult to establish universally accepted therapy guidelines. In this article we will review the evidence of the beta-blockers in heart failure in patients with congenital heart disease. Also we will discuss the mechanisms of heart failure in this patient's cohort and will review the literature with respect to the use of neurohormonal antagonists in congenital heart disease. There is an urgent need to initiate well-designed clinical trials to prove if the positive results of neurohormonal blockade in acquired heart failure in adults can be translated in patients with congenital heart disease.

Theory of mind deficit in adult patients with congenital heart disease.

PubMed

Chiavarino, Claudia; Bianchino, Claudia; Brach-Prever, Silvia; Riggi, Chiara; Palumbo, Luigi; Bara, Bruno G; Bosco, Francesca M

2015-10-01

This article provides the first assessment of theory of mind, that is, the ability to reason about mental states, in adult patients with congenital heart disease. Patients with congenital heart disease and matched healthy controls were administered classical theory of mind tasks and a semi-structured interview which provides a multidimensional evaluation of theory of mind (Theory of Mind Assessment Scale). The patients with congenital heart disease performed worse than the controls on the Theory of Mind Assessment Scale, whereas they did as well as the control group on the classical theory-of-mind tasks. These findings provide the first evidence that adults with congenital heart disease may display specific impairments in theory of mind. © The Author(s) 2013.

A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

EPA Science Inventory

Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

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

Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike

Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in anmore » apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to

Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

MedlinePlus

... Adult Diseases Resources Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English (US) Español (Spanish) ... important step in staying healthy. If you have cardiovascular disease, talk with your doctor about getting your vaccinations ...

Extra-cardiac manifestations of adult congenital heart disease.

PubMed

Gaeta, Stephen A; Ward, Cary; Krasuski, Richard A

2016-10-01

Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimating energy expenditure from heart rate in older adults: a case for calibration.

PubMed

Schrack, Jennifer A; Zipunnikov, Vadim; Goldsmith, Jeff; Bandeen-Roche, Karen; Crainiceanu, Ciprian M; Ferrucci, Luigi

2014-01-01

Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear. To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration. Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance. Heart rate and energy expenditure were highly correlated (r=0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. =0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min). These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration.

Perspectives of Puerto Rican Adults about Heart Health and a Potential Community Program

ERIC Educational Resources Information Center

Todorova, Irina L. G.; Tejada, Shirley; Castaneda-Sceppa, Carmen

2014-01-01

Background: Puerto Ricans are the second largest Hispanic group in the United States, and older adults have significant health disparities. Educational programs that address heart disease risk for this population have rarely been developed and implemented. Purpose: To address this gap, the Heart Healthy Initiative for Puerto Rican adults is being…

Zebrafish heart regeneration: 15 years of discoveries

PubMed Central

González‐Rosa, Juan Manuel; Burns, Caroline E.

2017-01-01

Abstract Cardiovascular disease is the leading cause of death worldwide. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart. This review provides a historical overview of adult zebrafish heart regeneration. We summarize 15 years of research, with a special focus on recent developments from this fascinating field. We discuss experimental findings that address fundamental questions of regeneration research. What is the origin of regenerated muscle? How is regeneration controlled from a genetic and molecular perspective? How do different cell types interact to achieve organ regeneration? Understanding natural models of heart regeneration will bring us closer to answering the ultimate question: how can we stimulate myocardial regeneration in humans? PMID:28979788

Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus

PubMed Central

Girardot, Fabrice; Péricard, Louise; Demeneix, Barbara A.; Coen, Laurent; Chai, Norin

2017-01-01

Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis. This method allowed in situ live heart observation, standardised tissue amputation size and reproducibility. During the first week following amputation, gene expression of cell proliferation markers remained unchanged, whereas those relating to sarcomere organisation decreased and markers of inflammation, fibrosis and hypertrophy increased. One-month post-amputation, fibrosis and hypertrophy were evident at the injury site, persisting through 11 months. Moreover, cardiomyocyte sarcomere organisation deteriorated early following amputation, and was not completely recovered as far as 11 months later. We conclude that the adult Xenopus heart is unable to regenerate, displaying cellular and molecular marks of scarring. Our work suggests that, contrary to urodeles and teleosts, with the exception of medaka, adult anurans share a cardiac injury outcome similar to adult mammals. This observation is at odds with current hypotheses that link loss of cardiac regenerative capacity with acquisition of homeothermy. PMID:28278282

Prominent mitochondrial DNA recombination intermediates in human heart muscle.

PubMed

Kajander, O A; Karhunen, P J; Holt, I J; Jacobs, H T

2001-11-01

Recombination intermediates containing four-way (Holliday) junctions are generated during DNA repair and replication in many systems, including yeast mitochondrial DNA (mtDNA). In contrast, convincing evidence for recombination in mammalian mtDNA is lacking. We have used two-dimensional agarose-gel electrophoresis to analyse non-linear forms of mtDNA in human heart muscle. Replication intermediates from both the coupled and strand-asynchronous mtDNA replication pathways were detected. An additional class of non-linear molecules, with the electrophoretic properties of four-way junctions, was also prominent. These molecules were insensitive to topoisomerase I or RNase H, but were diminished by branch migration or RuvC treatment. Junctional molecules were detected in all regions of the mitochondrial genome, were found in myocardial DNA from young and old adults, but were present at lower levels in skeletal muscle and placenta. We suggest that they could represent intermediates of mtDNA repair, given their prevalence in the oxyradical-rich environment of heart muscle mitochondria.

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts

PubMed Central

Chong, James J.H.; Yang, Xiulan; Don, Creighton W.; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M.; Van Biber, Benjamin; Cook, Savannah M.; Palpant, Nathan J; Gantz, Jay; Fugate, James A.; Muskheli, Veronica; Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A.; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.

2014-01-01

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure 1 by providing human cardiomyocytes to support heart regeneration 2. Studies of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in small animal models have shown favorable effects of this treatment 3–7. It remains unknown, however, whether clinical scale hESC-CMs transplantation is feasible, safe or can provide large-scale myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (>1 billion cells/batch) and cryopreserved with good viability. Using a non-human primate (NHP) model of myocardial ischemia-reperfusion, we show that that cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs generates significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a three-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small animal models 7, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome. PMID:24776797

Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

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

Weinberger, Florian, E-mail: f.weinberger@uke.de; Mehrkens, Dennis, E-mail: dennis.mehrkens@uk-koeln.de; Starbatty, Jutta, E-mail: starbatty@uke.uni-hamburg.de

Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activitymore » and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.« less

Choosing Between MRI and CT Imaging in the Adult with Congenital Heart Disease.

PubMed

Bonnichsen, Crystal; Ammash, Naser

2016-05-01

Improvements in the outcomes of surgical and catheter-based interventions and medical therapy have led to a growing population of adult patients with congenital heart disease. Adult patients with previously undiagnosed congenital heart disease or those previously palliated or repaired may have challenging echocardiographic examinations. Understanding the distinct anatomic and hemodynamic features of the congenital anomaly and quantifying ventricular function and valvular dysfunction plays an important role in the management of these patients. Rapid advances in imaging technology with magnetic resonance imaging (MRI) and computed tomography angiography (CTA) allow for improved visualization of complex cardiac anatomy in the evaluation of this unique patient population. Although echocardiography remains the most widely used imaging tool to evaluate congenital heart disease, alternative and, at times, complimentary imaging modalities should be considered. When caring for adults with congenital heart disease, it is important to choose the proper imaging study that can answer the clinical question with the highest quality images, lowest risk to the patient, and in a cost-efficient manner.

Congenital heart disease never goes away, even when it has been 'treated': the adult with congenital heart disease.

PubMed

Bhat, Aarti Hejmadi; Sahn, David J

2004-10-01

As the specialties of pediatrics and pediatric cardiology continue to forge ahead with better diagnoses, medical care, and surgical results, an expanding population of patients with congenital heart disease (CHD) outgrows the pediatric age group, yet does not quite graduate to routine adult cardiology or general medicine. The adult with congenital heart disease (ACHD) faces medical, surgical, and psychosocial issues that are unique to this population and must be addressed as such. This review attempts to discuss and highlight some of the important advances and controversies brought up in the past year, in the care and management of these patients. The past five to 10 years have seen dynamic interest in understanding sequelae of corrected, uncorrected, or palliated congenital heart disease. The search for the ideal surgery, optimal prosthesis, and a smooth transition to adult care continues and is reflected in the vast amount of academic work and publications in this field. Of particular interest, conduit reoperations and single ventricle pathway modifications are still an art and a science in evolution. While all are agreed that there is a pressing need to focus on the delivery of care to the adult with congenital heart disease, this essentially requires a clearer understanding of late sequelae of CHD. The sheer heterogeneity of anatomy, age, surgery, and institutional management protocols can make it difficult to develop clear guidelines. This review attempts to give an up-to-date perspective on some of the new findings related to the more common lesions and problems faced in this group.

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

PubMed

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

2017-01-01

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

Postoperative tricuspid regurgitation after adult congenital heart surgery is associated with adverse clinical outcomes.

PubMed

Lewis, Matthew J; Ginns, Jonathan N; Ye, Siqin; Chai, Paul; Quaegebeur, Jan M; Bacha, Emile; Rosenbaum, Marlon S

2016-02-01

Many patients with adult congenital heart disease will require cardiac surgery during their lifetime, and some will have concomitant tricuspid regurgitation. However, the optimal management of significant tricuspid regurgitation at the time of cardiac surgery remains unclear. We assessed the determinants of adverse outcomes in patients with adult congenital heart disease and moderate or greater tricuspid regurgitation undergoing cardiac surgery for non-tricuspid regurgitation-related indications. All adult patients with congenital heart disease and greater than moderate tricuspid regurgitation who underwent cardiac surgery for non-tricuspid regurgitation-related indications were included in a retrospective study at the Schneeweiss Adult Congenital Heart Center. Cohorts were defined by the type of tricuspid valve intervention at the time of surgery. The primary end point of interest was a composite of death, heart transplantation, and reoperation on the tricuspid valve. A total of 107 patients met inclusion criteria, and 17 patients (17%) reached the primary end point. A total of 68 patients (64%) underwent tricuspid valve repair, 8 patients (7%) underwent tricuspid valve replacement, and 31 patients (29%) did not have a tricuspid valve intervention. By multivariate analysis, moderate or greater postoperative tricuspid regurgitation was associated with a hazard ratio of 6.12 (1.84-20.3) for the primary end point (P = .003). In addition, failure to perform a tricuspid valve intervention at the time of surgery was associated with an odds ratio of 4.17 (1.26-14.3) for moderate or greater postoperative tricuspid regurgitation (P = .02). Moderate or greater postoperative tricuspid regurgitation was associated with an increased risk of death, transplant, or reoperation in adult patients with congenital heart disease undergoing cardiac surgery for non-tricuspid regurgitation-related indications. Concomitant tricuspid valve intervention at the time of cardiac surgery should

Imaging congenital heart disease in adults

PubMed Central

Kilner, P J

2011-01-01

Transthoracic echocardiography is the first-line modality for cardiovascular imaging in adults with congenital heart disease (ACHD). The windows of access that are possible with transthoracic echocardiography are, however, rarely adequate for all regions of interest. The choice of further imaging depends on the clinical questions that remain to be addressed. The strengths of MRI include comprehensive access and coverage, providing imaging of all parts of the right ventricle, the pulmonary arteries, pulmonary veins and aorta. Cine images and velocity maps are acquired in specifically aligned planes, with stacks of cines or dynamic contrast angiography providing more comprehensive coverage. Tissues can be characterised if necessary, and MRI provides relatively accurate measurements of biventricular function and volume flow. These parameters are important in the assessment and follow-up of adults after repairs for tetralogy of Fallot or transposition of the great arteries and after Fontan operations. The superior spatial resolution and rapid acquisition of CT are invaluable in selected situations, including the visualisation of anomalous coronary or aortopulmonary collateral arteries, the assessment of luminal patency after stenting and imaging in patients with pacemakers. Ionising radiation is, however, a concern in younger patients who may need repeated investigation. Adults with relatively complex conditions should ideally be imaged in a specialist ACHD centre, where dedicated echocardiographic and cardiovascular MRI services are a necessary facility. General radiologists should be aware of the nature and pathophysiology of congenital heart disease, and should be alert for previously undiagnosed cases presenting in adulthood, including cases of atrial septal defect, aortic coarctation, patent ductus arteriosus, double-chambered right ventricle and congenitally corrected transposition. PMID:22723533

ACE phenotyping in human heart.

PubMed

Tikhomirova, Victoria E; Kost, Olga A; Kryukova, Olga V; Golukhova, Elena Z; Bulaeva, Naida I; Zholbaeva, Aigerim Z; Bokeria, Leo A; Garcia, Joe G N; Danilov, Sergei M

2017-01-01

Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.

ACE phenotyping in human heart

PubMed Central

Tikhomirova, Victoria E.; Kost, Olga A.; Kryukova, Olga V.; Golukhova, Elena Z.; Bulaeva, Naida I.; Zholbaeva, Aigerim Z.; Bokeria, Leo A.; Garcia, Joe G. N.

2017-01-01

Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10–15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk. PMID:28771512

The quantitative assessment of epicardial fat distribution on human hearts: Implications for epicardial electrophysiology.

PubMed

Mattson, Alexander R; Soto, Mario J; Iaizzo, Paul A

2018-07-01

Epicardial electrophysiological procedures rely on dependable interfacing with the myocardial tissue. For example, epicardial pacing systems must generate sustainable chronic pacing capture, while epicardial ablations must effectively deliver energy to the target hyper-excitable myocytes. The human heart has a significant adipose layer which may impede epicardial procedures. The objective of this study was to quantitatively assess the relative location of epicardial adipose on the human heart, to define locations where epicardial therapies might be performed successfully. We studied perfusion-fixed human hearts (n = 105) in multiple isolated planes including: left ventricular margin, diaphragmatic surface, and anterior right ventricle. Relative adipose distribution was quantitatively assessed via planar images, using a custom-generated image analysis algorithm. In these specimens, 76.7 ± 13.8% of the left ventricular margin, 72.7 ± 11.3% of the diaphragmatic surface, and 92.1 ± 8.7% of the anterior right margin were covered with superficial epicardial adipose layers. Percent adipose coverage significantly increased with age (P < 0.001) and history of coronary artery disease (P < 0.05). No significant relationships were identified between relative percent adipose coverage and gender, body weight or height, BMI, history of hypertension, and/or history of congestive heart failure. Additionally, we describe two-dimensional probability distributions of epicardial adipose coverage for each of the three analysis planes. In this study, we detail the quantitative assessment and probabilistic mapping of the distribution of superficial epicardial adipose on the adult human heart. These findings have implications relative to performing epicardial procedures and/or designing procedures or tools to successfully perform such treatments. Clin. Anat. 31:661-666, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Perceptions about eating experiences of low-literate older adults with heart disease: a qualitative study.

PubMed

Chen, Su-Hui; Shyu, Yea-Ing Lotus; Ko, Yu-Shien; Kung, Hsiu Ling; Shao, Jung-Hua

2016-04-01

To explore perceptions of low-literate older adults with heart disease about their eating experiences. Heart disease has been closely linked with nutrition, and nutritional status is poor in patients with limited education, but no studies have explored the eating experiences of low-literate adults with heart disease. Qualitative descriptive study. Data were collected in tape-recorded semi-structured interviews from March-June 2012. A convenience sample of 13 low-literate older adults with heart disease was recruited from a cardiovascular ward of a medical centre in northern Taiwan. Participants were recruited until findings reached saturation and data were analysed using qualitative content analysis. Analysis of participants' interview data on eating experiences identified three main categories: (1) eating-related hardships because of low literacy; (2) eating adjustments due to low literacy; and (3) misinformation about dietary modifications for heart disease. Because of their low literacy, these older adults had difficult life experiences, gained inappropriate or inadequate eating information and held a passive, fatalistic perspective about eating with heart disease. Healthcare practitioners caring for this population need to appreciate their unique eating challenges and respect their eating customs. Nurses could play a greater role in educating and supporting low-literate older adults in selecting appropriate foods and preparing meals. Strategies to help this population learn to select, prepare and cook their food should be easy and practical, using specific symbols, concrete signs and simple labels. © 2016 John Wiley & Sons Ltd.

The power in being together for young adults who have heart disease - the photoshoot experience.

PubMed

Gallagher, Robyn; Potter, Ellen; Thomson Mangnall, Linda; Ladak, Laila; Gallagher, Patrick; Neubeck, Lis

The study aimed to determine perceived motivations and benefits of photoshoot participation for young adults who have heart disease. Feeling isolated and different can have lifelong affects on quality of life in heart disease survivors. Photoshoots, where people create a photographic image of themselves, promote positive interpretation of their cardiac illness experience, but participant experiences remain under-investigated. Young adult heart disease support group members completing a photoshoot were interviewed and data were thematically analyzed. Seven females and one male aged 20-47 years participated. The main theme, People Like Me, emphasized feelings of being different, isolated and uncertain due to the heart disease. Other themes related to support gained from people who were not like them, gaining and providing support to their peers. The photoshoot enabled a highly valued collective feeling. For young adult heart disease survivors, the photoshoot provides a fun, social opportunity to reduce isolation and share experiences. Copyright © 2017 Elsevier Inc. All rights reserved.

The Living Heart Project: A robust and integrative simulator for human heart function.

PubMed

Baillargeon, Brian; Rebelo, Nuno; Fox, David D; Taylor, Robert L; Kuhl, Ellen

2014-11-01

The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve.

Short-term outcomes following implementation of a dedicated young adult congenital heart disease transition program.

PubMed

Vaikunth, Sumeet S; Williams, Roberta G; Uzunyan, Merujan Y; Tun, Han; Barton, Cheryl; Chang, Philip M

2018-01-01

Transition from pediatric to adult care is a critical time for patients with congenital heart disease. Lapses in care can lead to poor outcomes, including increased mortality. Formal transition clinics have been implemented to improve success of transferring care from pediatric to adult providers; however, data regarding outcomes remain limited. We sought to evaluate outcomes of transfer within a dedicated transition clinic for young adult patients with congenital heart disease. We performed a retrospective analysis of all 73 patients seen in a dedicated young adult congenital heart disease transition clinic from January 2012 to December 2015 within a single academic institution that delivered pediatric and adult care at separate children's and adult hospitals, respectively. Demographic characteristics including congenital heart disease severity, gender, age, presence of comorbidities, presence of cardiac implantable electronic devices, and type of insurance were correlated to success of transfer. Rate of successful transfer was evaluated, and multivariate analysis was performed to determine which demographic variables were favorably associated with transfer. Thirty-nine percent of patients successfully transferred from pediatric to adult services during the study period. Severe congenital heart disease (OR 4.44, 95% CI 1.25-15.79, P = .02) and presence of a cardiac implantable electronic device (OR 4.93, 95% CI 1.18-20.58, P = .03) correlated with transfer. Trends favoring successful transfer with presence of comorbidities and private insurance were also noted. Despite a dedicated transition clinic, successful transfer rates remained relatively low though comparable to previously published rates. Severity of disease and presence of implantable devices correlated with successful transfer. Other obstacles to transfer remain and require combined efforts from pediatric and adult care systems, insurance carriers, and policy makers to improve transfer outcomes. �

[Adult congenital heart disease: Medical and psychosocial issues].

PubMed

Ladouceur, Magalie; Pontnau, Florence; Iserin, Laurence

2017-05-01

The population of adults with congenital heart disease (ACHD) is continuously increasing with now a higher prevalence than that of the pediatric population. This concerns above all complex congenital heart diseases. Heart failure is the primary cause of death followed by arrhythmia, which is very common in ACHD. A specialized follow-up by dedicated centers is significantly associated with an improvement of survival of ACHD patients compared to non-expert follow-up. Extracardiac disorders (liver, kidney, respiratory) are frequent and require an accurate and specific management. The psychosocial impact, particularly the professional difficulties, is common and may require implementation of appropriate measures to improve the patient social life. Unplanned pregnancy and/or a lack of information about contraception may induce severe cardiovascular complications in ACHD women. Education about contraceptive methods at adolescence and pre-conceptional counseling are requested in this population. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

PubMed Central

Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

2017-01-01

Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

PubMed

Rorabaugh, Boyd R; Seeley, Sarah L; Stoops, Thorne S; D'Souza, Manoranjan S

2017-01-01

We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

Lifestyle Habits among Adult Congenital Heart Disease Patients in Malta.

PubMed

Caruana, Maryanne; Grech, Victor

2016-07-01

Adult congenital heart disease patients are prone to health risk behaviors like their peers. Such behaviors can have serious implications, particularly in patients with complex congenital lesions. We investigated patterns in tobacco smoking, alcohol consumption, substance misuse, dental reviews, and physical activity in Maltese patients. A questionnaire modeled on the 2008 European Health Interview Survey was offered to consecutive adult congenital heart disease outpatients, aged 16 years and over, between May 2013 and May 2014. Foreigners and patients with learning difficulties or cognitive impairment were excluded. Data on these habits was compared with that from 372 age-matched and sex-matched 2008 survey responders (general population cohort). There were 125 patient responders (65 males; mean age 30.64, SD 12.80 years). Adult congenital heart disease patients smoked less (patients 18.4%, general 32.0% P = .004) and had more regular dental reviews (patients 60.9%, general 45.2% P = .003) but were less physically active than the general population cohort (patients 30.6%, general 62.9% P < .001). The difference in smoking was only significant in patients born after the mid-1970s (younger) and females, while dental reviews were only better in younger and male patients. Male patients consumed alcohol more frequently (38.1%) than general population males (23.3%, P = .02). In the patient cohort, smoking was more likely with milder congenital lesions (OR 4.689, P = .007), substance misuse more likely in males (OR 5.703, P = .036) and with milder lesions (OR 5.405, P = .030) and alcohol consumption more likely in males (OR 11.697, P < .001). Although there is an overall lower uptake of some unhealthy habits by Maltese adult congenital heart disease patients, this is not consistent between sexes or age groups. Male and older patients and those with milder lesions might need more reinforcement of the advice given regarding lifestyle habits

Electrocardiographic Findings in Brazilian Adults without Heart Disease: ELSA-Brasil.

PubMed

Pinto, Marcelo Martins; Brant, Luisa C C; Padilha-da-Silva, José Luiz; Foppa, Murilo; Lotufo, Paulo A; Mill, José Geraldo; Vasconcelo-Silva, Paulo R; Almeida, Maria da Conceição C; Barreto, Sandhi Maria; Ribeiro, Antônio Luiz Pinho

2017-11-01

The electrocardiogram (ECG) is widely used in population-based studies. However, there are few studies on electrocardiographic findings in Latin America and in Brazil. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) comprised 15,105 participants (35-74 years) from six Brazilian capitals. To describe electrocardiographic findings in Brazilian adults without heart disease, stratified by sex, age and race/skin color. Cross-sectional study with baseline data of 11,094 adults (44.5% men) without heart disease from ELSA-Brasil. The ECGs were recorded with the Burdick Atria 6100 machine and stored at the Pyramis System. ECG analysis was automatically performed using the Glasgow University software. A descriptive analysis of heart rate (HR), P, QRS and T waves' duration, PR and QT intervals, and P, R and T axes was performed. After stratification by sex, race/color and age, the groups were compared by the Wilcoxon and Kruskal-Wallis test at a significance level of 5%. Linear regression models were used to evaluate the behavior of electrocardiographic parameters over age. Major electrocardiographic abnormalities defined by the Minnesota code were manually revised. Medians values of the electrocardiographic parameters were different between men and women: HR 63 vs. 66 bpm, PR 164 vs.158 ms, QT corrected 410 vs. 421 ms, QRS duration 92 vs. 86 ms, P-wave duration 112 vs. 108 ms, P-wave axis 54 vs. 57 degrees, R-wave axis 35 vs. 39 degrees, T-wave axis 39 vs. 45 degrees (p < 0.001 for all). The 2nd and the 98th percentiles of each variable were also obtained, and graphs were constructed to illustrate the behavior of the electrocardiographic findings over age of participants stratified by sex and race/skin color. The values for the electrocardiographic measurements herein described can be used as reference for Brazilian adults free of heart disease, stratified by sex. Our results suggest that self-reported race/skin color have no significant influence on

Electrocardiographic Findings in Brazilian Adults without Heart Disease: ELSA-Brasil

PubMed Central

Pinto Filho, Marcelo Martins; Brant, Luisa C. C.; Padilha-da-Silva, José Luiz; Foppa, Murilo; Lotufo, Paulo A.; Mill, José Geraldo; Vasconcelo-Silva, Paulo R.; Almeida, Maria da Conceição C.; Barreto, Sandhi Maria; Ribeiro, Antônio Luiz Pinho

2017-01-01

Background The electrocardiogram (ECG) is widely used in population-based studies. However, there are few studies on electrocardiographic findings in Latin America and in Brazil. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) comprised 15,105 participants (35-74 years) from six Brazilian capitals. Objectives To describe electrocardiographic findings in Brazilian adults without heart disease, stratified by sex, age and race/skin color. Methods Cross-sectional study with baseline data of 11,094 adults (44.5% men) without heart disease from ELSA-Brasil. The ECGs were recorded with the Burdick Atria 6100 machine and stored at the Pyramis System. ECG analysis was automatically performed using the Glasgow University software. A descriptive analysis of heart rate (HR), P, QRS and T waves’ duration, PR and QT intervals, and P, R and T axes was performed. After stratification by sex, race/color and age, the groups were compared by the Wilcoxon and Kruskal-Wallis test at a significance level of 5%. Linear regression models were used to evaluate the behavior of electrocardiographic parameters over age. Major electrocardiographic abnormalities defined by the Minnesota code were manually revised. Results Medians values of the electrocardiographic parameters were different between men and women: HR 63 vs. 66 bpm, PR 164 vs.158 ms, QT corrected 410 vs. 421 ms, QRS duration 92 vs. 86 ms, P-wave duration 112 vs. 108 ms, P-wave axis 54 vs. 57 degrees, R-wave axis 35 vs. 39 degrees, T-wave axis 39 vs. 45 degrees (p < 0.001 for all). The 2nd and the 98th percentiles of each variable were also obtained, and graphs were constructed to illustrate the behavior of the electrocardiographic findings over age of participants stratified by sex and race/skin color. Conclusions The values for the electrocardiographic measurements herein described can be used as reference for Brazilian adults free of heart disease, stratified by sex. Our results suggest that self-reported race

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

PubMed

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

2017-05-01

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

High resource use among adult congenital heart surgery admissions in adult hospitals: risk factors and association with death and comorbidities.

PubMed

Bhatt, Ami B; Rajabali, Alefiyah; He, Wei; Benavidez, Oscar J

2015-01-01

Adult hospitals are a common location of adult congenital heart disease (ACHD) admissions, including cardiac surgical admissions. Understanding the patterns and predictors of resource use could aid these institutions by identifying and targeting potentially modifiable determinants of high resource use (HRU). Our objectives were to examine resource use during adult congenital heart surgical admissions in adult hospitals, determine the association of HRU with mortality, and identify risk factors for HRU. Population-based retrospective study We obtained data from the Nationwide Inpatient Sample 2005-2009 and examined ACHD surgical admissions ages 18-49 years (n = 16 231). We defined HRU as admissions with >90th percentile for total hospital charges. Despite representing 10% of admissions, HRU admissions accounted for 32% of total charges. HRU admissions had a higher mortality rate (9.7% vs. 1.8%, P < .001). Multivariable analysis demonstrated that HRU is associated with government insurance adjusted odds ratio (AOR) 2.0 (95% confidence interval [CI] 1.6,2.4), emergency admissions AOR 3.9 (95% CI 3.1,4.8), complications AOR 4.2 (95% CI 3.3,5.2), renal failure AOR 1.8 (95% CI 1.4,2.2), congestive heart failure AOR 1.2 (95% CI 1,1.4), surgical complexity risk category-2 AOR 2.0 (95% CI 1.0,3.6), and category-3+ AOR 2.3 (95% CI 1.4,3.8). HRU admissions for adult congenital heart surgery consumed a disproportionate amount of resources and were associated with higher mortality. HRU risk factors included nonelective admissions, government insurance, heart failure, surgical complexity, renal failure, and complications. Complications, if preventable, may be a target for improvement strategies to decrease resource use. Other risk factors may require a broader patient care approach. © 2014 Wiley Periodicals, Inc.

Sports participation in adults with congenital heart disease.

PubMed

Opić, Petra; Utens, Elisabeth M W J; Cuypers, Judith A A E; Witsenburg, Maarten; van den Bosch, Annemien; van Domburg, Ron; Bogers, Ad J J C; Boersma, Eric; Pelliccia, Antonio; Roos-Hesselink, Jolien W

2015-01-01

It is unclear whether sports participation in adults with repaired congenital heart disease is safe and has benefits. Congenital heart disease (ConHD) patients who underwent corrective surgery for Atrial Septal Defect, Ventricular Septal Defect, Pulmonary Stenosis, Tetralogy of Fallot or Transposition of the Great Arteries in our center between 1968 and 1980 were included, and participated in our longitudinal follow-up study with serial evaluations in 2001 and 2011. At both time points patients filled in questionnaires on sports participation, subjective physical functioning and quality of life. Exercise testing, echocardiogram and 24-hour continuous ambulatory ECG-monitoring were performed in both 2001 and 2011. All clinical events (re-intervention, arrhythmia, heart failure) were prospectively recorded. No relationship was found between practicing sports and the occurrence of sudden death, PVCs or SVTs. Patients with moderate/complex forms of ConHD practiced fewer hours of sports compared with the general Dutch normative population. Patients with both simple and moderate/complex ConHD who practiced sports showed a higher exercise capacity. More favorable subjective physical functioning was found for moderate/complex patients who practiced sports. Adults with repaired ConHD are less often involved in sports than the Dutch general population. The patients that were engaged in sports show a higher exercise capacity than those who did not. Sports participation in patients with ConHD was not associated with an increased incidence of adverse cardiac events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phase Transition in a Healthy Human Heart Rate

NASA Astrophysics Data System (ADS)

Kiyono, Ken; Struzik, Zbigniew R.; Aoyagi, Naoko; Togo, Fumiharu; Yamamoto, Yoshiharu

2005-07-01

A healthy human heart rate displays complex fluctuations which share characteristics of physical systems in a critical state. We demonstrate that the human heart rate in healthy individuals undergoes a dramatic breakdown of criticality characteristics, reminiscent of continuous second order phase transitions. By studying the germane determinants, we show that the hallmark of criticality—highly correlated fluctuations—is observed only during usual daily activity, and a breakdown of these characteristics occurs in prolonged, strenuous exercise and sleep. This finding is the first reported discovery of the dynamical phase transition phenomenon in a biological control system and will be a key to understanding the heart rate control system in health and disease.

Successful cardiac transplantation outcomes in patients with adult congenital heart disease.

PubMed

Menachem, Jonathan N; Golbus, Jessica R; Molina, Maria; Mazurek, Jeremy A; Hornsby, Nicole; Atluri, Pavan; Fuller, Stephanie; Birati, Edo Y; Kim, Yuli Y; Goldberg, Lee R; Wald, Joyce W

2017-09-01

The purpose of our study is (1) to characterise patients with congenital heart disease undergoing heart transplantation by adult cardiac surgeons in a large academic medical centre and (2) to describe successful outcomes associated with our multidisciplinary approach to the evaluation and treatment of adults with congenital heart disease (ACHD) undergoing orthotopic heart transplantation (OHT). Heart failure is the leading cause of death in patients with ACHD leading to increasing referrals for OHT. The Penn Congenital Transplant Database comprises a cohort of patients with ACHD who underwent OHT between March 2010 and April 2016. We performed a retrospective cohort study of the 20 consecutive patients. Original cardiac diagnoses include single ventricle palliated with Fontan (n=8), dextro-transposition of the great arteries after atrial switch (n=4), tetralogy of Fallot (n=4), pulmonary atresia (n=1), Ebstein anomaly (n=1), unrepaired ventricular septal defect (n=1) and Noonan syndrome with coarctation of the aorta (n=1). Eight patients required pretransplant inotropes and two required pretransplant mechanical support. Nine patients underwent heart-liver transplant and three underwent heart-lung transplant. Three patients required postoperative mechanical circulatory support. Patients were followed for an average of 38 months as of April 2016, with 100% survival at 30 days and 1 year and 94% overall survival (19/20 patients). ACHD-OHT patients require highly specialised, complex and multidisciplinary healthcare. The success of our programme is attributed to using team-based, patient-centred care including our multidisciplinary staff and specialists across programmes and departments. © 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.

From adolescents to adults with congenital heart disease: the role of transition.

PubMed

Moceri, Pamela; Goossens, Eva; Hascoet, Sebastien; Checler, Carine; Bonello, Béatrice; Ferrari, Emile; Acar, Philippe; Fraisse, Alain

2015-07-01

Improved surgical care during the last decades, together with advances in medical management, led to a remarkable increase in survival of patients with congenital heart disease (CHD). However, aging of the CHD population brings new challenges, and loss of follow-up of adolescents and adults with CHD is a major concern. It is crucial to optimize the transfer of patients with CHD from paediatric to adult health care services to prevent loss to follow-up. The transition process plays a central role in the future health and follow-up of the patient. The aim of this review is to explain and discuss the clinical impact of the transition process in adolescents with CHD. We will also discuss specific CHD adolescents' problems. Adolescence is a crucial phase for the formation of the personality. Understanding and acceptance of the responsibility for health at this stage through a transition process with a multidisciplinary team will determine the quality of future medical follow-up and probably limit psychosocial issues in their adult life. • Aging of the congenital heart disease population brings new challenges to the organisation of care. • Loss of follow-up is a major concern for patients with congenital heart disease. What is new: • The quality of a formal transition process during adolescence will determine future outcomes in patients with congenital heart disease.

Predictors of influenza vaccination uptake among adults with a history of heart attack.

PubMed

Jiménez-García, Rodrigo; Hernández-Barrera, Valentín; de Andres, Ana Lopez; Jimenez-Trujillo, Isabel; Esteban, Jesus; Gil, Angel; Carrasco-Garrido, Pilar

2010-07-01

Influenza vaccination can reduce morbidity and mortality caused by cardiovascular diseases. This study sought to evaluate influenza vaccination coverage among adults with a history of heart attack and to determine which variables were associated with vaccine uptake. A total of 716 adults reported having suffered a heart attack. The coverage among sufferers was 67.9% as against 35% for non sufferers. The variables that were significantly associated with a higher likelihood of receiving the vaccine among sufferers were: higher age; male gender, no smoking habit, "Physician visits in the preceding four weeks"; and, "Blood pressure control in the preceding three months". A descriptive study was conducted using individual data from adults aged ≥40 years included in the year 2006/7 Spanish Health Survey and comparing subjects with a history of heart attack with those who had not suffered this event. The number of participants surveyed was 20,060. Subjects were classified as heart attack sufferers if they answered affirmatively to the question: "Has your doctor told you that you have suffered a heart attack?" To assess influenza vaccination status we considered the response to the question, "Did you have a 'flu shot in the latest campaign?". Independent variables included sociodemographic, health-related, lifestyles and periodic control of cardiovascular risk factors. Influenza vaccination coverage among subjects who have suffered a heart attack is below desirable levels. Multiple strategies focused on providers and patients are needed to improve influenza vaccination coverage among these high risk subjects, particularly now with the emerging H1N1 pandemic.

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts.

PubMed

Garreta, Elena; de Oñate, Lorena; Fernández-Santos, M Eugenia; Oria, Roger; Tarantino, Carolina; Climent, Andreu M; Marco, Andrés; Samitier, Mireia; Martínez, Elena; Valls-Margarit, Maria; Matesanz, Rafael; Taylor, Doris A; Fernández-Avilés, Francisco; Izpisua Belmonte, Juan Carlos; Montserrat, Nuria

2016-08-01

Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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.

Association between resting heart rate, metabolic syndrome and cardiorespiratory fitness in Korean male adults.

PubMed

Kang, Seol-Jung; Ha, Gi-Chul; Ko, Kwang-Jun

2017-06-01

The present study aimed to investigate the association between metabolic syndrome and cardiorespiratory fitness according to resting heart rate of Korean male adults. A total of 11,876 male adults aged 20-65 years who underwent health examinations from 2010 to 2015 at a National Fitness Centre in South Korea were included. Subjects' resting heart rate, cardiorespiratory fitness (VO 2 max), and metabolic syndrome parameters were collected. The subjects were divided into 5 categories (<60 bpm, 60-69 bpm, 70-79 bpm, 80-89 bpm, and ≥90 bpm) of resting heart rate for further analysis. We found that elevated resting heart rate was positively associated with body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, and fasting blood glucose levels ( p  < 0.001, respectively); in contrast, elevated resting heart rate was inversely associated with VO 2 max ( p  < 0.001). When resting heart rate of subjects was categorized into quintiles and analysed, the results showed that the relative risk of metabolic syndrome was 1.53-fold higher (95% CI, 1.34 to 1.82) in the range of 60-69 beats per minute (bpm), 2.08-fold higher (95% CI, 1.77 to 2.45) in the range of 70-79 bpm, 2.28-fold higher (95% CI, 1.73 to 3.00) in the range of 80-89 bpm, and 2.61-fold higher (95% CI, 1.62 to 4.20) in the range of ≥90 bpm, compared to those <60 bpm; this indicated that as resting heart rate increased, the relative risk of metabolic syndrome also increased. Resting heart rate of male adults was found to be associated with cardiorespiratory fitness; the risk factors for metabolic syndrome and relative risk of metabolic syndrome increased as resting heart rate increased.

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.

Time-lapse imaging of human heart motion with switched array UWB radar.

PubMed

Brovoll, Sverre; Berger, Tor; Paichard, Yoann; Aardal, Øyvind; Lande, Tor Sverre; Hamran, Svein-Erik

2014-10-01

Radar systems for detection of human heartbeats have mostly been single-channel systems with limited spatial resolution. In this paper, a radar system for ultra-wideband (UWB) imaging of the human heart is presented. To make the radar waves penetrate the human tissue the antenna is placed very close to the body. The antenna is an array with eight elements, and an antenna switch system connects the radar to the individual elements in sequence to form an image. Successive images are used to build up time-lapse movies of the beating heart. Measurements on a human test subject are presented and the heart motion is estimated at different locations inside the body. The movies show rhythmic motion consistent with the beating heart, and the location and shape of the reflections correspond well with the expected response form the heart wall. The spatial dependent heart motion is compared to ECG recordings, and it is confirmed that heartbeat modulations are seen in the radar data. This work shows that radar imaging of the human heart may provide valuable information on the mechanical movement of the heart.

Medication regimen complexity in ambulatory older adults with heart failure.

PubMed

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

2017-01-01

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

The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

PubMed

Dos Remedios, C G; Lal, S P; Li, A; McNamara, J; Keogh, A; Macdonald, P S; Cooke, R; Ehler, E; Knöll, R; Marston, S B; Stelzer, J; Granzier, H; Bezzina, C; van Dijk, S; De Man, F; Stienen, G J M; Odeberg, J; Pontén, F; Linke, W; van der Velden, J

2017-08-01

The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are

The Evolution of an Adult Congenital Heart Surgery Program: The Emory System.

PubMed

Kogon, Brian; Rosenblum, Joshua; Alsoufi, Bahaaldin; Shashidharan, Subhadra; Book, Wendy

2017-01-01

The Emory Adult Congenital Heart (Emory University, Atlanta, GA) program was founded in 2001. In 2004, the surgical component transitioned from a pediatric facility to an adult facility. The aim of this article is characterize the program as a whole, outline changes in the program, and discuss the challenges of the transition process. Between 2001 and 2015, changes in program structure and personnel were evaluated. There has been significant growth of the program between 2001 and 2015. There are currently 19 half-day clinics per week, with 2,700 clinic visits per year. There are six cardiologists, three congenital cardiac surgeons, two sonographers, one advanced practice provider, and one social worker dedicated to the program. There are Accreditation Council for Graduate Medical Education-accredited adult congenital cardiology and congenital cardiac surgery fellowships. One thousand forty-four operations were performed between 2001 and 2015. There were 828 open-heart operations, of which 581 (70%) were re-operations. Over the study period, the number of yearly operations increased from 30 to 119, and the mean age at surgery increased from 22 to 35 years. Over time, more of the operations were performed at the adult hospital: increasing from 3% in 2001 to 82% in 2015, and more of the operations were performed by congenital cardiac surgeons: 87% (114 of 131) before the 2004 transition to 97% (881 of 913) afterward. The Emory Adult Congenital Heart program has undergone significant growth and change, including transition of the surgical component from the pediatric to the adult facility. While numerous obstacles have been overcome and great progress has been made, additional challenges remain. Copyright © 2017 Elsevier Inc. All rights reserved.

Can stem cells really regenerate the human heart? Use your noggin, dickkopf! Lessons from developmental biology.

PubMed

Sommer, Paula

2013-06-01

The human heart is the first organ to develop and its development is fairly well characterised. In theory, the heart has the capacity to regenerate, as its cardiomyocytes may be capable of cell division and the adult heart contains a cardiac stem cell niche, presumably capable of differentiating into cardiomyocytes and other cardiac-associated cell types. However, as with most other organs, these mechanisms are not activated upon serious injury. Several experimental options to induce regeneration of the damaged heart tissue are available: activate the endogenous cardiomyocytes to divide, coax the endogenous population of stem cells to divide and differentiate, or add exogenous cell-based therapy to replace the lost cardiac tissue. This review is a summary of the recent research into all these avenues, discussing the reasons for the limited successes of clinical trials using stem cells after cardiac injury and explaining new advances in basic science. It concludes with a reiteration that chances of successful regeneration would be improved by understanding and implementing the basics of heart development and stem cell biology.

Adults with an epilepsy history, notably those 45-64 years old or at the lowest income levels, more often report heart disease than adults without an epilepsy history.

PubMed

Zack, Matthew; Luncheon, Cecily

2018-06-13

From 95,196 sample adults in the combined 2010, 2013, and 2015 U.S. National Health Interview Survey, we estimated the association between histories of epilepsy and heart disease after accounting for sociodemographic characteristics and behavioral risk factors. Adults 18 years old or older with an epilepsy history reported heart disease (21%) about nine percentage points more often than those without such a history (12%), overall and within levels of characteristics and risk factors. These increases in heart disease history for adults with an epilepsy history compared with adults without such a history were greater in those 45-64 years old or at the lowest family income levels. These increases of heart disease in adults with an epilepsy history highlight two needs-to prevent the occurrence of heart disease and to reduce its consequences. Because comorbidity from heart disease can complicate epilepsy management, physicians caring for those with epilepsy should be aware of these increased risks, identify risk factors for heart disease, and recommend to their patients with epilepsy ways to diminish these risks. Copyright © 2018 Elsevier Inc. All rights reserved.

Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

PubMed

Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

2015-08-24

Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2011-01-01

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

Variability in heart rate recovery measurements over 1 year in healthy, middle-aged adults.

PubMed

Mellis, M G; Ingle, L; Carroll, S

2014-02-01

This study assessed the longer-term (12-month) variability in post-exercise heart rate recovery following a submaximal exercise test. Longitudinal data was analysed for 97 healthy middle-aged adults (74 male, 23 female) from 2 occasions, 12 months apart. Participants were retrospectively selected if they had stable physical activity habits, submaximal treadmill fitness and anthropometric measurements between the 2 assessment visits. A submaximal Bruce treadmill test was performed to at least 85% age-predicted maximum heart rate. Absolute heart rate and Δ heart rate recovery (change from peak exercise heart rate) were recorded for 1 and 2 min post-exercise in an immediate supine position. Heart rate recovery at both time-points was shown to be reliable with intra-class correlation coefficient values ≥ 0.714. Absolute heart rate 1-min post-exercise showed the strongest agreement between repeat tests (r = 0.867, P < 0.001). Lower coefficient of variation (≤ 10.2%) and narrower limits of agreement were found for actual heart rate values rather than Δ heart rate recovery, and for 1-min rather than 2-min post-exercise recovery time points. Log-transformed values generated better variability with acceptable coefficient of variation for all measures (2.2-10%). Overall, 1 min post-exercise heart rate recovery data had least variability over the 12-month period in apparently healthy middle-aged adults. © Georg Thieme Verlag KG Stuttgart · New York.

Exercise-based cardiac rehabilitation for adults after heart valve surgery.

PubMed

Sibilitz, Kirstine L; Berg, Selina K; Tang, Lars H; Risom, Signe S; Gluud, Christian; Lindschou, Jane; Kober, Lars; Hassager, Christian; Taylor, Rod S; Zwisler, Ann-Dorthe

2016-03-21

Exercise-based cardiac rehabilitation may benefit heart valve surgery patients. We conducted a systematic review to assess the evidence for the use of exercise-based intervention programmes following heart valve surgery. To assess the benefits and harms of exercise-based cardiac rehabilitation compared with no exercise training intervention, or treatment as usual, in adults following heart valve surgery. We considered programmes including exercise training with or without another intervention (such as a psycho-educational component). We searched: the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS (Bireme); and Conference Proceedings Citation Index-S (CPCI-S) on Web of Science (Thomson Reuters) on 23 March 2015. We handsearched Web of Science, bibliographies of systematic reviews and trial registers (ClinicalTrials.gov, Controlled-trials.com, and The World Health Organization International Clinical Trials Registry Platform). We included randomised clinical trials that investigated exercise-based interventions compared with no exercise intervention control. The trial participants comprised adults aged 18 years or older who had undergone heart valve surgery for heart valve disease (from any cause) and received either heart valve replacement, or heart valve repair. Two authors independently extracted data. We assessed the risk of systematic errors ('bias') by evaluation of bias risk domains. Clinical and statistical heterogeneity were assessed. Meta-analyses were undertaken using both fixed-effect and random-effects models. We used the GRADE approach to assess the quality of evidence. We sought to assess the risk of random errors with trial sequential analysis. We included two trials from 1987 and 2004 with a total 148 participants who have had heart valve surgery. Both trials had a high risk of bias.There was insufficient evidence

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.

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

Illness, normality and identity: the experience of heart transplant as a young adult.

PubMed

Waldron, Rebecca; Malpus, Zoey; Shearing, Vanessa; Sanchez, Melissa; Murray, Craig D

2017-09-01

End stage heart failure and transplant present great opportunities and challenges for patients of all ages. However, young adulthood may present additional specific challenges associated with the development of identity, career and romantic relationships. Despite recognition of greater mortality rates in young adults, consideration of the experience of transplant during this life stage has been largely overlooked in the literature. The aim of this study was to explore the experience of heart transplant in young adults. Interviews were conducted with nine participants across three transplant services in the United Kingdom and the data subject to interpretative phenomenological analysis. Analysis identified three themes. "Separating from illness" and "working toward normality" involved limiting the influence of illness on identity, as well as reengaging with typical functioning in young adulthood. "Integrating transplant into identity" involved acknowledging the influence of living with a shortened life expectancy. The need for support that recognizes specific challenges of transplant as a young adult is discussed (e.g. the development of age specific end of life pathways, improved communication between transplant recipients, their families and teams), including consideration of the impact of societal discourses (e.g. gift of life) which provided additional challenges for patients. IMPLICATIONS FOR REHABILITATION Heart transplant presents specific challenges according to the recipient's life stage. The needs of young adult recipients should be considered. Transplant professionals should consider providing opportunities for peer support and addressing the identities and values of young adult transplant recipients during rehabilitation.

Clinical Research Priorities in Adult Congenital Heart Disease

PubMed Central

Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R.; John, Anitha S.; Valente, Anne Marie; Zaidi, Ali N.; Cook, Stephen C.; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J.; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S.

2014-01-01

Background Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. Methods A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. Results The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. Conclusions The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. PMID:24411207

Clinical research priorities in adult congenital heart disease.

PubMed

Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R; John, Anitha S; Valente, Anne Marie; Zaidi, Ali N; Cook, Stephen C; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S

2014-02-15

Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Alternative Splicing of NOX4 in the Failing Human Heart

PubMed Central

Varga, Zoltán V.; Pipicz, Márton; Baán, Júlia A.; Baranyai, Tamás; Koncsos, Gábor; Leszek, Przemyslaw; Kuśmierczyk, Mariusz; Sánchez-Cabo, Fátima; García-Pavía, Pablo; Brenner, Gábor J.; Giricz, Zoltán; Csont, Tamás; Mendler, Luca; Lara-Pezzi, Enrique; Pacher, Pál; Ferdinandy, Péter

2017-01-01

Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions) were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation. Deep RNA sequencing of the cardiac transcriptome indicated extensive alternative splicing of the NOX4 gene in heart failure as compared to samples from healthy donor hearts. Long distance PCR analysis with a universal 5′-3′ end primer pair, allowing amplification of different splice variants, confirmed the presence of the splice variants. To assess translation of the alternatively spliced transcripts we determined protein expression of NOX4 by using a specific antibody recognizing a conserved region in all variants. Western blot analysis showed up-regulation of the full-length NOX4 in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms both in control and failing samples with disease-associated expression pattern. We describe here for the first time that NOX4 undergoes extensive alternative splicing in human hearts which gives rise to the expression of different enzyme isoforms. The full length NOX4 is significantly upregulated in ischemic cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure. PMID:29204124

Human heart conjugate cooling simulation: Unsteady thermo-fluid-stress analysis

PubMed Central

Abdoli, Abas; Dulikravich, George S.; Bajaj, Chandrajit; Stowe, David F.; Jahania, M. Salik

2015-01-01

The main objective of this work was to demonstrate computationally that realistic human hearts can be cooled much faster by performing conjugate heat transfer consisting of pumping a cold liquid through the cardiac chambers and major veins while keeping the heart submerged in cold gelatin filling a cooling container. The human heart geometry used for simulations was obtained from three-dimensional, high resolution MRI scans. Two fluid flow domains for the right (pulmonic) and left (systemic) heart circulations, and two solid domains for the heart tissue and gelatin solution were defined for multi-domain numerical simulation. Detailed unsteady temperature fields within the heart tissue were calculated during the conjugate cooling process. A linear thermoelasticity analysis was performed to assess the stresses applied on the heart due to the coolant fluid shear and normal forces and to examine the thermal stress caused by temperature variation inside the heart. It was demonstrated that a conjugate cooling effort with coolant temperature at +4°C is capable of reducing the average heart temperature from +37°C to +8°C in 25 minutes for cases in which the coolant was steadily pumped only through major heart inlet veins and cavities. PMID:25045006

Abnormal lung function in adults with congenital heart disease: prevalence, relation to cardiac anatomy, and association with survival.

PubMed

Alonso-Gonzalez, Rafael; Borgia, Francesco; Diller, Gerhard-Paul; Inuzuka, Ryo; Kempny, Aleksander; Martinez-Naharro, Ana; Tutarel, Oktay; Marino, Philip; Wustmann, Kerstin; Charalambides, Menelaos; Silva, Margarida; Swan, Lorna; Dimopoulos, Konstantinos; Gatzoulis, Michael A

2013-02-26

Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (P=0.04). A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.

Effect of fetal hypoxia on heart susceptibility to ischemia and reperfusion injury in the adult rat.

PubMed

Li, Guohu; Xiao, Yuhui; Estrella, Jaymie L; Ducsay, Charles A; Gilbert, Raymond D; Zhang, Lubo

2003-07-01

Epidemiologic studies showed an association between adverse intrauterine environment and ischemic heart disease in the adult. We tested the hypothesis that prenatal hypoxia increased the susceptibility of adult heart to ischemia-reperfusion (I-R) injury. Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% oxygen from day 15 to 21) groups. Hearts of 6-month-old male progeny were studied using Langendorff preparation and were subjected to two protocols of I-R: 10 minutes of ischemia and 3 hours of reperfusion (I-R(10)) or 25 minutes of ischemia and 3 hours of reperfusion (I-R(25)). Prenatal hypoxia did not change basal left ventricular (LV) function. I-R(10) produced myocardial stunning and a transient decrease in LV function in control hearts but caused myocardial infarction and a persistent decrease in postischemic recovery of LV function in hypoxic hearts. I-R(25) caused myocardial infarction in both control and hypoxic hearts, which was significantly higher in hypoxic hearts. The postischemic recovery of LV function was significantly reduced in hypoxic hearts. I-R(25)-induced activation of caspase-3 and apoptosis in the left ventricle were significantly higher in hypoxic than control hearts. There was a significant decrease in LV heat shock protein 70 and endothelial nitric oxide synthase levels in hypoxic hearts. Prenatal hypoxia did not change beta(1)-adrenoreceptor levels but significantly increased beta(2)-adrenoreceptor in the left ventricle. In addition, it increased G(s)alpha but decreased G(i)alpha. Prenatal chronic hypoxia increases the susceptibility of adult heart to I-R injury. Several possible mechanisms may be involved, including an increase in beta(2)-adrenoreceptor and the G(s)alpha/G(i)alpha ratio, and a decrease in heat shock protein 70 and endothelial nitric oxide synthase in the left ventricle.

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

PubMed

Lui, George K; Saidi, Arwa; Bhatt, Ami B; Burchill, Luke J; Deen, Jason F; Earing, Michael G; Gewitz, Michael; Ginns, Jonathan; Kay, Joseph D; Kim, Yuli Y; Kovacs, Adrienne H; Krieger, Eric V; Wu, Fred M; Yoo, Shi-Joon

2017-11-14

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention. © 2017 American Heart Association, Inc.

Are urinary polyaromatic hydrocarbons associated with adult hypertension, heart attack, and cancer? USA NHANES, 2011-2012.

PubMed

Shiue, Ivy

2015-11-01

Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols and pesticides. Therefore, it was aimed to study the relationships of urinary polyaromatic hydrocarbons and adult cardiovascular disease and cancer using human sample in a national and population-based study in recent years. Data was retrieved from US National Health and Nutrition Examination Surveys, 2011-2012, including demographics, self-reported health conditions and urinary polyaromatic hydrocarbons. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary polyaromatic hydrocarbons (representatively in one-third sample) were observed to be higher in people with cardiovascular disease and total cancer. In particular, urinary 4-hydroxyphenanthrene was associated with hypertension (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.00-1.76, P = 0.048, PAR 5.1%), urinary 1-hydroxypyrene was significantly associated with heart attack (OR 1.47, 95%CI 1.05-2.06, P = 0.027, PAR 1.7%), and urinary 2-hydroxynapthalene (2-naphthol) was associated with cancer (OR 1.46, 95%CI 1.12-1.90, P = 0.008, PAR 3.9%). Urinary polyaromatic hydrocarbons were associated with adult hypertension, heart attack and cancer, although the causality cannot be established. From the research perspective, future studies with a longitudinal or experimental approach would be suggested. From the law and public health perspectives, regulation on minimizing exposure to polyaromatic hydrocarbons might need to be considered in future health and environmental policies and intervention programs.

Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure.

PubMed

Vegter, Eline L; Ovchinnikova, Ekaterina S; Silljé, Herman H W; Meems, Laura M G; van der Pol, Atze; van der Velde, A Rogier; Berezikov, Eugene; Voors, Adriaan A; de Boer, Rudolf A; van der Meer, Peter

2017-01-01

We recently identified a set of plasma microRNAs (miRNAs) that are downregulated in patients with heart failure in comparison with control subjects. To better understand their meaning and function, we sought to validate these circulating miRNAs in 3 different well-established rat and mouse heart failure models, and correlated the miRNAs to parameters of cardiac function. The previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-199a-3p, miR-223-3p, miR-423-3p, miR-423-5p and miR-652-3p were measured by means of quantitative real time polymerase chain reaction (qRT-PCR) in plasma samples of 8 homozygous TGR(mREN2)27 (Ren2) transgenic rats and 8 (control) Sprague-Dawley rats, 6 mice with angiotensin II-induced heart failure (AngII) and 6 control mice, and 8 mice with ischemic heart failure and 6 controls. Circulating miRNA levels were compared between the heart failure animals and healthy controls. Ren2 rats, AngII mice and mice with ischemic heart failure showed clear signs of heart failure, exemplified by increased left ventricular and lung weights, elevated end-diastolic left ventricular pressures, increased expression of cardiac stress markers and reduced left ventricular ejection fraction. All miRNAs were detectable in plasma from rats and mice. No significant differences were observed between the circulating miRNAs in heart failure animals when compared to the healthy controls (all P>0.05) and no robust associations with cardiac function could be found. The previous observation that miRNAs circulate in lower levels in human patients with heart failure could not be validated in well-established rat and mouse heart failure models. These results question the translation of data on human circulating miRNA levels to experimental models, and vice versa the validity of experimental miRNA data for human heart failure.

Advances in the Care of Adults With Congenital Heart Disease.

PubMed

Nasr, Viviane G; Kussman, Barry D

2015-09-01

The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. © The Author(s) 2014.

Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

PubMed

Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

2017-05-09

Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

Consecutive Isoproterenol and Adenosine Treatment Confers Marked Protection against Reperfusion Injury in Adult but Not in Immature Heart: A Role for Glycogen.

PubMed

Lewis, Martin; Szobi, Adrian; Balaska, Dirki; Khaliulin, Igor; Adameova, Adriana; Griffiths, Elinor; Orchard, Clive H; Suleiman, M-Saadeh

2018-02-07

Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff-perfused hearts from adult and immature (60 and 14 days old) male Wistar rats were exposed to 30 min ischemia and 120 min reperfusion, with or without prior perfusion with 5 nM Iso for 3 min followed by 30 μM Aden for 5 min. Changes in hemodynamics (developed pressure and coronary flow) and cardiac injury (Lactate Dehydrogenase (LDH) release and infarct size) were measured. Additional hearts were used to measure glycogen content. Iso induced a similar inotropic response in both age groups. Treatment with Iso/Aden resulted in a significant reduction in time to the onset of ischemic contracture in both age groups whilst time to peak contracture was significantly shorter only in immature hearts. Upon reperfusion, the intervention reduced cardiac injury and functional impairment in adults with no protection of immature heart. Immature hearts have significantly less glycogen content compared to adult. This work shows that Iso/Aden perfusion confers protection in an adult heart but not in an immature heart. It is likely that metabolic differences including glycogen content contribute to this difference.

Causes of death in a contemporary adult congenital heart disease cohort.

PubMed

Yu, Christopher; Moore, Benjamin M; Kotchetkova, Irina; Cordina, Rachael L; Celermajer, David S

2018-04-17

The life expectancy of patients with congenital heart disease (CHD) has significantly improved with advances in their paediatric medical care. Mortality patterns are changing as a result. Our study aims to describe survival and causes of death in a contemporary cohort of adult patients with CHD. We reviewed 3068 patients in our adult CHD database (age ≥16 years, seen at least once in our centre between 2000 and 2015), and documented the number and causes of death, via Australia's National Death Index. Survival and mortality patterns were analysed by complexity of CHD and by underlying congenital diagnosis. Our cohort comprised 3068 adult patients (53% male). The distribution of patients (per the Bethesda classification) was 47% simple, 34% moderate and 18% complex (1% not classifiable). Over a median follow-up of 6.2 years (IQR 3.5-10.4), 341 patients (11%) died with an incidence of 0.4 deaths/100 patient years (py). Survival was significantly worse with increasing complexity of CHD (p<0.001); mortality rate in the simple group was 0.3 deaths/100 py with a median age of death 70 years, and in the complex group was 1.0 death/100 py with a median age of death 34 years. Overall, non-cardiac causes of death outnumbered cardiac causes, at 54% and 46%, respectively. The leading single cause of death was heart failure (17%), followed by malignancy (13%). Simple adult CHD patients mostly died due to non-cardiac causes such as malignancy. Perioperative mortality only accounted for 5% of deaths. Premature death is common in adults with CHD. Although heart failure remains the most common cause of death, in the contemporary era in a specialist CHD centre, non-cardiac related deaths outnumber cardiac deaths, particularly in those with simple CHD lesions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves.

PubMed

Peña-Silva, Ricardo A; Miller, Jordan D; Chu, Yi; Heistad, Donald D

2009-10-01

Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2*.-) was measured in heart valves from explanted human hearts that were not used for transplantation. (O2*.-) levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in (O2*.-). Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased (O2*.-) levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in (O2*.-) during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated (O2*.-), and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.

Early Parenthood as a Link between Childhood Disadvantage and Adult Heart Problems: A Gender-Based Approach

PubMed Central

Lee, Chioun; Ryff, Carol D.

2016-01-01

Drawing on conceptual models of critical periods, major life transitions, and life pathways, we proposed that the life-course features of parenthood are important, but understudied, mechanisms for explaining possibly gendered heart-health outcomes. Using three waves from the Midlife in the U.S. Study (MIDUS), we investigated (a) gender differences in the timing of the transition to parenthood as a pathway linking childhood SES disadvantage to onset of heart problems and (b) life-course factors (which vary by gender) that link the timing of the transition to parenthood to adult heart problems. We found that individuals who were disadvantaged in childhood were more likely to have their first child as teenagers or in early young adulthood. For women only, an early transition to parenthood partially explained the association between childhood disadvantage and onset of heart problems. Furthermore, women who had their first child at younger ages, particularly in their teens, had lower rates of college graduation, more financial difficulties, higher levels of depressive symptoms, and greater risk of smoking and obesity in midlife. These factors partially accounted for the association between early parenthood and onset of heart problems in later life. Our findings underscore the significance of the timing of the transition to parenthood in specifying the associations between childhood disadvantage and adult heart problems. Various factors are involved, including low adult SES, psychological distress, and unhealthy lifestyles. PMID:27823815

Knowledge of heart attack and stroke symptomology: a cross-sectional comparison of rural and non-rural US adults.

PubMed

Swanoski, Michael T; Lutfiyya, May Nawal; Amaro, Maria L; Akers, Michael F; Huot, Krista L

2012-06-01

Understanding the signs and symptoms of heart attacks and strokes are important not only in saving lives, but also in preserving quality of life. Findings from recent research have yielded that the prevalence of cardiovascular disease risk factors are higher in rural populations, suggesting that adults living in rural locales may be at higher risk for heart attack and/or stroke. Knowledge of heart attack and stroke symptomology as well as calling 911 for a suspected heart attack or stroke are essential first steps in seeking care. This study sought to examine the knowledge of heart attack and stroke symptoms among rural adults in comparison to non-rural adults living in the U.S. Using multivariate techniques, a cross-sectional analysis of an amalgamated multi-year Behavioral Risk Factor Surveillance Survey (BRFSS) database was performed. The dependent variable for this analysis was low heart attack and stroke knowledge score. The covariates for the analysis were: age, sex, race/ethnicity, annual household income, attained education, health insurance status, having a health care provider (HCP), timing of last routine medical check-up, medical care deferment because of cost, self-defined health status and geographic locale. The weighted n for this study overall was 103,262,115 U.S. adults  > =18 years of age. Approximately 22.0% of these respondents were U.S. adults living in rural locales. Logistic regression analysis revealed that those U.S. adults who had low composite heart attack and stroke knowledge scores were more likely to be rural (OR=1.218 95%CI 1.216-1.219) rather than non-rural residents. Furthermore, those with low scores were more likely to be: male (OR=1.353 95%CI 1.352-1.354), >65 years of age (OR=1.369 95%CI 1.368-1.371), African American (OR=1.892 95%CI 1.889-1.894), not educated beyond high school (OR=1.400 955CI 1.399-1.402), uninsured (OR=1.308 95%CI 1.3-6-1.310), without a HCP (OR=1.216 95%CI 1.215-1.218), and living in a household with an

Medication management strategies used by older adults with heart failure: A systems-based analysis.

PubMed

Mickelson, Robin S; Holden, Richard J

2017-09-01

Older adults with heart failure use strategies to cope with the constraining barriers impeding medication management. Strategies are behavioral adaptations that allow goal achievement despite these constraining conditions. When strategies do not exist, are ineffective or maladaptive, medication performance and health outcomes are at risk. While constraints to medication adherence are described in literature, strategies used by patients to manage medications are less well-described or understood. Guided by cognitive engineering concepts, the aim of this study was to describe and analyze the strategies used by older adults with heart failure to achieve their medication management goals. This mixed methods study employed an empirical strategies analysis method to elicit medication management strategies used by older adults with heart failure. Observation and interview data collected from 61 older adults with heart failure and 31 caregivers were analyzed using qualitative content analysis to derive categories, patterns and themes within and across cases. Data derived thematic sub-categories described planned and ad hoc methods of strategic adaptations. Stable strategies proactively adjusted the medication management process, environment, or the patients themselves. Patients applied situational strategies (planned or ad hoc) to irregular or unexpected situations. Medication non-adherence was a strategy employed when life goals conflicted with medication adherence. The health system was a source of constraints without providing commensurate strategies. Patients strived to control their medication system and achieve goals using adaptive strategies. Future patient self-mangement research can benefit from methods and theories used to study professional work, such as strategies analysis.

Self-efficacy as a predictor of patient-reported outcomes in adults with congenital heart disease.

PubMed

Thomet, Corina; Moons, Philip; Schwerzmann, Markus; Apers, Silke; Luyckx, Koen; Oechslin, Erwin N; Kovacs, Adrienne H

2018-04-01

Self-efficacy is a known predictor of patient-reported outcomes in individuals with acquired diseases. With an overall objective of better understanding patient-reported outcomes in adults with congenital heart disease, this study aimed to: (i) assess self-efficacy in adults with congenital heart disease, (ii) explore potential demographic and medical correlates of self-efficacy and (iii) determine whether self-efficacy explains additional variance in patient-reported outcomes above and beyond known predictors. As part of a large cross-sectional international multi-site study (APPROACH-IS), we enrolled 454 adults (median age 32 years, range: 18-81) with congenital heart disease in two tertiary care centres in Canada and Switzerland. Self-efficacy was measured using the General Self-Efficacy (GSE) scale, which produces a total score ranging from 10 to 40. Variance in the following patient-reported outcomes was assessed: perceived health status, psychological functioning, health behaviours and quality of life. Hierarchical multivariable linear regression analysis was performed. Patients' mean GSE score was 30.1 ± 3.3 (range: 10-40). Lower GSE was associated with female sex ( p = 0.025), not having a job ( p = 0.001) and poorer functional class ( p = 0.048). GSE positively predicted health status and quality of life, and negatively predicted symptoms of anxiety and depression, with an additional explained variance up to 13.6%. No associations between self-efficacy and health behaviours were found. GSE adds considerably to our understanding of patient-reported outcomes in adults with congenital heart disease. Given that self-efficacy is a modifiable psychosocial factor, it may be an important focus for interventions targeting congenital heart disease patients' well-being.

The Medicare Drug Benefit (Part D) and Treatment of Heart Failure in Older Adults

PubMed Central

Donohue, Julie M.; Zhang, Yuting; Lave, Judith R.; Gellad, Walid F.; Men, Aiju; Perera, Subashan; Hanlon, Joseph T.

2010-01-01

Background Adherence to pharmacotherapy for heart failure is poor among older adults due, in part, to high prescription drug costs. We examined the impact of improvements in drug coverage under Medicare Part D on utilization of, and adherence to, medications for heart failure in older adults. Methods We used a quasi-experimental approach to analyze pharmacy claims for 6,950 individuals age≥65 years with heart failure enrolled in a Medicare managed care organization two years before and after Part D’s implementation. We compared prescription fill patterns among individuals who moved from limited (quarterly benefits caps of $150 or $350) or no drug coverage to Part D in 2006 to those who had generous employer-sponsored coverage throughout the study period. Results Individuals who previously lacked drug coverage filled approximately 6 more heart failure prescriptions annually after Part D (Adjusted Ratio of Prescription Counts = 1.36, 95% Confidence Interval=CI=1.29-1.44; p<0.0001 relative to the comparison group). Those previously lacking drug coverage were more likely to fill prescriptions for an angiotensin converting enzyme inhibitor/angiotensin II receptor blocker plus a beta blocker after Part D (adjusted ratio of odds ratios=AROR=1.73; 95% CI=1.42-2.10; p<0.0001), and more likely to be adherent to such pharmacotherapy (AROR=2.95; 95% CI=1.85-4.69; p<0.0001) relative to the comparison group. Conclusions Medicare Part D was associated with improved access to medications and adherence to pharmacotherapy in older adults with heart failure. PMID:20598987

Prevalence of HCV Infection in Adults with Congenital Heart Disease and Treatment with Direct Antiviral Agents.

PubMed

Gade, Ajay Reddy; Patel, Manisha; West, Donna R; Abrams, Gary A

2018-03-01

Hepatitis C virus (HCV) infection affects >3% of the US population, which over time can lead to cirrhosis and hepatocellular carcinoma. The lack of a reliable screening method for HCV before 1992 resulted in a higher prevalence of the virus in adults with congenital heart disease who underwent corrective surgery that required blood transfusions. Direct-acting antiviral agents such as sofosbuvir/ledipasvir have significantly increased the efficacy of HCV therapy, although use of these medications in adults with congenital heart disease has not been described. Ours was a retrospective study of 188 adults with congenital heart conditions who had cardiac surgery before 1992. These patients were screened for HCV using HCV antibody followed by HCV RNA if the screening test was positive. Of the 188 adults, 116 (43% male patients, 24-70 years) were screened for the HCV antibody, demonstrating that 104 individuals were negative and 12 subjects were positive for the virus. Subsequently, further testing for the presence of HCV demonstrated 11 of 12 were infected, with an overall prevalence of 9.5%. Five individuals chose to be treated with sofosbuvir/ledipasvir and 5 of 5 have successfully cleared the virus and are considered cured. Adults with congenital heart disease who underwent cardiac surgery before 1992 warrant being screened for HCV, and, if testing positive, may be considered for therapy using direct-acting antiviral agents with close monitoring for cardiac complications.

Cardiac Arrhythmias in Adults With Congenital Heart Disease: Scope, Specific Problems, and Management.

PubMed

Lindsay, Ian; Moore, Jeremy P

2015-12-01

Progressive advances in the field of congenital heart disease (CHD) have led to a dramatic rise in the number of affected patients surviving well into adulthood. Groundbreaking and innovative achievements in the medical, surgical, and interventional management of these patients have allowed them to lead full adult lives that have included raising families, completing degrees in higher education, and maintaining successful careers. As patients are living longer, arrhythmias have emerged as one of the most significant factors affecting their morbidity, mortality, and quality of life. This article aims to review the current understanding of arrhythmia within the adult congenital heart disease (ACHD) population, emphasizing recent advances and providing recommendations pertaining to the management of these patients.

Current Role of Blood and Urine Biomarkers in the Clinical Care of Adults with Congenital Heart Disease.

PubMed

Rajpal, Saurabh; Alshawabkeh, Laith; Opotowsky, Alexander R

2017-06-01

There is an increasing number of adult patients with congenital heart disease (CHD). While several biomarkers have been validated and integrated into general cardiology clinical practice, these tests are often applied to adults with CHD in the absence of disease-specific validation. Although these patients are often grouped into a single population, there is heterogeneous pathophysiology, variable disease chronicity, extensive multisystem involvement, and a low event rate relative to acquired heart disease. These stand as challenges to systematic investigation and clinical application of biomarkers for adults with CHD. This paper reviews recent studies investigating the use of biomarkers in this population, with emphasis on biomarkers applied in clinical adult CHD care. A handful of biomarkers have been integrated into adult CHD practice, such as iron studies in cyanotic heart disease and stool alpha-1 antitrypsin for diagnosis of protein losing enteropathy in the Fontan circulation. Use of kidney and liver tests has been studied in prognostication of adult CHD patients. A few other biomarkers like natriuretic peptides and troponins seem likely to provide useful information in other ACHD situations based on limited disease-specific data and extrapolation from acquired heart disease. More research is needed to support the robust validity of most existing clinical biomarkers in adult congenital cardiology practice. Until data from larger, prospectively enrolled cohorts are available, clinical use of biomarkers in these patients will require careful interpretation with attention to underlying pathophysiology, as well as detailed understanding of potential pitfalls of specific assays and clinical contexts.

Consecutive Isoproterenol and Adenosine Treatment Confers Marked Protection against Reperfusion Injury in Adult but Not in Immature Heart: A Role for Glycogen

PubMed Central

Szobi, Adrian; Balaska, Dirki; Khaliulin, Igor; Adameova, Adriana; Griffiths, Elinor; Orchard, Clive H.; Suleiman, M.-Saadeh

2018-01-01

Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff–perfused hearts from adult and immature (60 and 14 days old) male Wistar rats were exposed to 30 min ischemia and 120 min reperfusion, with or without prior perfusion with 5 nM Iso for 3 min followed by 30 μM Aden for 5 min. Changes in hemodynamics (developed pressure and coronary flow) and cardiac injury (Lactate Dehydrogenase (LDH) release and infarct size) were measured. Additional hearts were used to measure glycogen content. Iso induced a similar inotropic response in both age groups. Treatment with Iso/Aden resulted in a significant reduction in time to the onset of ischemic contracture in both age groups whilst time to peak contracture was significantly shorter only in immature hearts. Upon reperfusion, the intervention reduced cardiac injury and functional impairment in adults with no protection of immature heart. Immature hearts have significantly less glycogen content compared to adult. This work shows that Iso/Aden perfusion confers protection in an adult heart but not in an immature heart. It is likely that metabolic differences including glycogen content contribute to this difference. PMID:29414860

MRI Detects Myocardial Iron in the Human Heart

PubMed Central

Ghugre, Nilesh R.; Enriquez, Cathleen M.; Gonzalez, Ignacio; Nelson, Marvin D.; Coates, Thomas D.; Wood, John C.

2010-01-01

Iron-induced cardiac dysfunction is a leading cause of death in transfusion-dependent anemia. MRI relaxation rates R2(1/T2) and R2∗(1∕T2∗) accurately predict liver iron concentration, but their ability to predict cardiac iron has been challenged by some investigators. Studies in animal models support similar R2 and R2∗ behavior with heart and liver iron, but human studies are lacking. To determine the relationship between MRI relaxivities and cardiac iron, regional variations in R2 and R2∗ were compared with iron distribution in one freshly deceased, unfixed, iron-loaded heart. R2 and R2∗ were proportionally related to regional iron concentrations and highly concordant with one another within the interventricular septum. A comparison of postmortem and in vitro measurements supports the notion that cardiac R2∗ should be assessed in the septum rather than the whole heart. These data, along with measurements from controls, provide bounds on MRI-iron calibration curves in human heart and further support the clinical use of cardiac MRI in iron-overload syndromes. PMID:16888797

The heart rate response to nintendo wii boxing in young adults.

PubMed

Bosch, Pamela R; Poloni, Joseph; Thornton, Andrew; Lynskey, James V

2012-06-01

To determine if 30 minutes of Nintendo Wii Sports boxing provides cardiorespiratory benefits and contributes to the daily exercise recommendations for healthy young adults. Twenty healthy 23- to 27-year-olds participated in two sessions to measure maximum heart rate (HR(max)) via a treadmill test and heart rate (HR) response to 30 minutes of Wii Sports boxing. Heart rate in beats per minute (bpm) was measured continuously, and exercise intensity during each minute of play was stratified as a percentage of HR(max). Mixed designs analysis of variance (ANOVA) and Pearson product moment correlations were used to analyze the data. Mean (SD) HR response to boxing was 143 (15) bpm or 77.5% (10.0%) of HR(max). The mean HR response for experienced participants was significantly lower than inexperienced participants, P = .007. The ANOVA revealed a significant interaction between experience and time spent at various intensities, P = .009. Experienced participants spent more time in light to vigorous intensities, inexperienced participants in moderate to very hard intensities. Fitness was not correlated with mean HR response to boxing, P = .49. Thirty minutes of Nintendo Wii Sports boxing provides a moderate to vigorous aerobic response in healthy young adults and can contribute to daily recommendations for physical activity.

The Heart Rate Response to Nintendo Wii Boxing in Young Adults

PubMed Central

Bosch, Pamela R.; Poloni, Joseph; Thornton, Andrew; Lynskey, James V.

2012-01-01

Purpose To determine if 30 minutes of Nintendo Wii Sports boxing provides cardiorespiratory benefits and contributes to the daily exercise recommendations for healthy young adults. Methods Twenty healthy 23- to 27-year-olds participated in two sessions to measure maximum heart rate (HRmax) via a treadmill test and heart rate (HR) response to 30 minutes of Wii Sports boxing. Heart rate in beats per minute (bpm) was measured continuously, and exercise intensity during each minute of play was stratified as a percentage of HRmax. Mixed designs analysis of variance (ANOVA) and Pearson product moment correlations were used to analyze the data. Results Mean (SD) HR response to boxing was 143 (15) bpm or 77.5% (10.0%) of HRmax. The mean HR response for experienced participants was significantly lower than inexperienced participants, P = .007. The ANOVA revealed a significant interaction between experience and time spent at various intensities, P = .009. Experienced participants spent more time in light to vigorous intensities, inexperienced participants in moderate to very hard intensities. Fitness was not correlated with mean HR response to boxing, P = .49. Conclusion Thirty minutes of Nintendo Wii Sports boxing provides a moderate to vigorous aerobic response in healthy young adults and can contribute to daily recommendations for physical activity. PMID:22833705

Adult congenital heart disease in Greece: Preliminary data from the CHALLENGE registry.

PubMed

Giannakoulas, G; Vasiliadis, K; Frogoudaki, A; Ntellos, C; Tzifa, A; Brili, S; Manginas, A; Papaphylactou, M; Parcharidou, D; Kampouridis, N; Pitsis, A; Chamaidi, A; Kolios, M; Papadopoulos, G; Douras, A; Davlouros, P; Ntiloudi, D; Karvounis, H; Kalangos, A; Tsioufis, C; Rammos, S

2017-10-15

The majority of patients with congenital heart disease (CHD), nowadays, survives into adulthood and is faced with long-term complications. We aimed to study the basic demographic and clinical characteristics of adult patients with congenital heart disease (ACHD) in Greece. A registry named CHALLENGE (Adult Congenital Heart Disease Registry. A registry from Hellenic Cardiology Society) was initiated in January 2012. Patients with structural CHD older than 16years old were enrolled by 16 specialized centers nationwide. Out of a population of 2115 patients with ACHD, who have been registered, (mean age 38years (SD 16), 52% women), 47% were classified as suffering from mild, 37% from moderate and 15% from severe ACHD. Atrial septal defect (ASD) was the most prevalent diagnosis (33%). The vast majority of ACHD patients (92%) was asymptomatic or mildly symptomatic (NYHA class I/II). The most symptomatic patients were suffering from an ASD, most often the elderly or those under targeted therapy for pulmonary arterial hypertension. Elderly patients (>60years old) accounted for 12% of the ACHD population. Half of patients had undergone at least one open-heart surgery, while 39% were under cardiac medications (15% under antiarrhythmic drugs, 16% under anticoagulants, 16% under medications for heart failure and 4% under targeted therapy for pulmonary arterial hypertension). ACHD patients are an emerging patient population and national prospective registries such as CHALLENGE are of unique importance in order to identify the ongoing needs of these patients and match them with the appropriate resource allocation. Copyright © 2017 Elsevier B.V. All rights reserved.

Racial disparities in knowledge of stroke and heart attack risk factors and warning signs among Michigan adults.

PubMed

Fussman, Chris; Rafferty, Ann P; Reeves, Mathew J; Zackery, Shannon; Lyon-Callo, Sarah; Anderson, Beth

2009-01-01

To describe the level of knowledge regarding risk factors and warning signs for stroke and heart attack among White and African American adults in Michigan and to quantify racial disparities. Knowledge of stroke and heart attack risk factors and warning signs was assessed by using data from the 2004 Michigan Behavioral Risk Factor Survey. Prevalence estimates of knowledge were generated, and statistical differences in knowledge between Whites and African Americans were assessed. Adequate knowledge was defined as knowing 3 correct warning signs or risk factors. Logistic regression models were used to quantify the racial disparity in knowledge while controlling for potential confounding. Whites had substantially higher levels of adequate knowledge of risk factors (stroke: 31.6% vs 13.8%; heart attack: 52.6% vs 24.3%) and warning signs (stroke: 30.0% vs 17.2%; heart attack: 29.3% vs 13.8%) compared with African Americans (all observed differences were significant at P < .05). The odds of adequate knowledge of risk factors (stroke: adjusted odds ratio [AOR] 2.9; heart attack: AOR 3.4) and warning signs (stroke: AOR 2.0; heart attack: AOR 2.4) were significantly higher for Whites than for African Americans. A strong racial disparity in the knowledge of stroke and heart attack risk factors and warning signs exists among Michigan adults. Communitywide public education programs in conjunction with targeted interventions for at-risk populations are necessary to produce meaningful improvements in the awareness of stroke and heart attack risk factors and warning signs among Michigan adults.

Adult congenital heart disease nurse coordination: Essential skills and role in optimizing team-based care a position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

PubMed

Sillman, Christina; Morin, Joanne; Thomet, Corina; Barber, Deena; Mizuno, Yoshiko; Yang, Hsiao-Ling; Malpas, Theresa; Flocco, Serena Francesca; Finlay, Clare; Chen, Chi-Wen; Balon, Yvonne; Fernandes, Susan M

2017-02-15

Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with congenital heart disease (CHD) worldwide. Among ISACHD's objectives is to "promote a holistic team-based approach to the care of the adult with CHD that is comprehensive, patient-centered, and interdisciplinary" (http://www.isachd.org). This emphasis on team-based care reflects the fact that adults with CHD constitute a heterogeneous population with a wide spectrum of disease complexity, frequent association with other organ involvement, and varied co-morbidities and psychosocial issues. Recognizing the vital role of the adult CHD (ACHD) nurse coordinator (ACHD-NC) in optimizing team-based care, ISACHD established a task force to elucidate and provide guidance on the roles and responsibilities of the ACHD-NC. Acknowledging that nursing roles can vary widely from region to region based on factors such as credentials, scopes of practice, regulations, and local culture and tradition, an international panel was assembled with experts from North America, Europe, East Asia, and Oceania. The writing committee was tasked with reviewing key aspects of the ACHD-NC's role in team-based ACHD care. The resulting ISACHD position statement addresses the ACHD-NC's role and skills required in organizing, coordinating, and facilitating the care of adults with CHD, holistic assessment of the ACHD patient, patient education and counseling, and support for self-care management and self-advocacy. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Methods to assess Drosophila heart development, function and aging

PubMed Central

Ocorr, Karen; Vogler, Georg; Bodmer, Rolf

2014-01-01

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

Attributing heart attack and stroke to "Old Age": Implications for subsequent health outcomes among older adults.

PubMed

Stewart, Tara L; Chipperfield, Judith G; Perry, Raymond P; Hamm, Jeremy M

2016-01-01

This study assessed the extent to which older adults attribute a recent heart attack/stroke to "old age," and examined consequences for subsequent lifestyle behavior and health-care service utilization. Community-dwelling adults (N = 57, ages 73-98 years) were interviewed about their heart attack/stroke, and an objective health registry provided data on health-care utilization over a 3-year period. Endorsement of "old age" as a cause of heart attack/stroke negatively predicted lifestyle behavior change, and positively predicted frequency of physician visits and likelihood of hospitalization over the subsequent 3 years. Findings suggest the importance of considering "old age" attributions in the context of cardiovascular health events. © The Author(s) 2014.

Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure

PubMed Central

Lou, Qing; Fedorov, Vadim V.; Glukhov, Alexey V.; Moazami, Nader; Fast, Vladimir G.; Efimov, Igor R.

2011-01-01

Background Excitation-contraction (EC) coupling is altered in the end-stage heart failure (HF). However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective is to study functional remodeling of EC coupling and calcium handling in failing and nonfailing human hearts. Methods and Results We simultaneously optically mapped action potentials (AP) and calcium transients (CaT) in coronary-perfused left ventricular wedge preparations from nonfailing (n = 6) and failing (n = 5) human hearts. Our major findings are: (1) CaT duration minus AP duration was longer at sub-endocardium in failing compared to nonfailing hearts during bradycardia (40 beats/min). (2) The transmural gradient of CaT duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 beats/min). (3) CaT in failing hearts had a flattened plateau at the midmyocardium; and exhibited a “two-component” slow rise at sub-endocardium in three failing hearts. (4) CaT relaxation was slower at sub-endocardium than that at sub-epicardium in both groups. Protein expression of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) was lower at sub-endocardium than that at sub-epicardium in both nonfailing and failing hearts. SERCA2a protein expression at sub-endocardium was lower in hearts with ischemic cardiomyopathy compared with nonischemic cardiomyopathy. Conclusions For the first time, we present direct experimental evidence of transmural heterogeneity of EC coupling and calcium handling in human hearts. End-stage HF is associated with the heterogeneous remodeling of EC coupling and calcium handling. PMID:21502574

Clinical Experience With the Subcutaneous Implantable Cardioverter-Defibrillator in Adults With Congenital Heart Disease.

PubMed

Moore, Jeremy P; Mondésert, Blandine; Lloyd, Michael S; Cook, Stephen C; Zaidi, Ali N; Pass, Robert H; John, Anitha S; Fish, Frank A; Shannon, Kevin M; Aboulhosn, Jamil A; Khairy, Paul

2016-09-01

Sudden cardiac death is a major contributor to mortality for adults with congenital heart disease. The subcutaneous implantable cardioverter-defibrillator (ICD) has emerged as a novel tool for prevention of sudden cardiac death, but clinical performance data for adults with congenital heart disease are limited. A retrospective study involving 7 centers over a 5-year period beginning in 2011 was performed. Twenty-one patients (median 33.9 years) were identified. The most common diagnosis was single ventricle physiology (52%), 9 palliated by Fontan operation and 2 by aortopulmonary shunts: d-transposition of the great arteries after Mustard/Senning (n=2), tetralogy of Fallot (n=2), aortic valve disease (n=2), and other biventricular surgery (n=4). A prior cardiac device had been implanted in 7 (33%). The ICD indication was primary prevention in 67% and secondary in 33% patients. The most common reason for subcutaneous ICD placement was limited transvenous access for ventricular lead placement (n=10) followed by intracardiac right-to-left shunt (n=5). Ventricular arrhythmia was induced in 17 (81%) and was converted with ≤80 Joules in all. There was one implant complication related to infection, not requiring device removal. Over a median follow-up of 14 months, 4 patients (21%) received inappropriate and 1 (5%) patient received appropriate shocks. There was one arrhythmic death related to asystole in a single ventricle patient. Subcutaneous ICD implantation is feasible for adults with congenital heart disease patients. Most candidates have single ventricle heart disease and limited transvenous options for ICD placement. Despite variable anatomy, this study demonstrates successful conversion of induced ventricular arrhythmia and reasonable rhythm discrimination during follow-up. © 2016 American Heart Association, Inc.

Successful treatment of heart failure in an adult patient with Prader-Willi syndrome.

PubMed

Kawano, Hiroaki; Ikeda, Tooru; Shimazaki, Koichi; Arakawa, Shuji; Matsumoto, Yuji; Hayano, Motonobu; Maemura, Koji

2013-01-01

Prader-Willi Syndrome (PWS) is a rare genetic disorder characterized by physical, psychological and physiological abnormalities. Obesity and related cardiovascular diseases are a common problem in adult patients with PWS. This report describes a case of adult PWS with heart failure associated with marked obesity and sleep-disordered breathing that was successfully treated with oxygen therapy, adaptive servoventilation, medications, diet therapy and rehabilitation.

Implementation of the American College of Cardiology/American Heart Association 2008 Guidelines for the Management of Adults With Congenital Heart Disease.

PubMed

Goossens, Eva; Fernandes, Susan M; Landzberg, Michael J; Moons, Philip

2015-08-01

Although different guidelines on adult congenital heart disease (ACHD) care advocate for lifetime cardiac follow-up, a critical appraisal of the guideline implementation is lacking. We investigated the implementation of the American College of Cardiology/American Heart Association 2008 guidelines for ACHD follow-up by investigating the type of health care professional, care setting, and frequency of outpatient visits in young adults with CHD. Furthermore, correlates for care in line with the recommendations or untraceability were investigated. A cross-sectional observational study was conducted, including 306 patients with CHD who had a documented outpatient visit at pediatric cardiology before age 18 years. In all, 210 patients (68.6%) were in cardiac follow-up; 20 (6.5%) withdrew from follow-up and 76 (24.9%) were untraceable. Overall, 198 patients were followed up in tertiary care, 1/4 (n = 52) of which were seen at a formalized ACHD care program and 3/4 (n = 146) remained at pediatric cardiology. Of those followed in formalized ACHD and pediatric cardiology care, the recommended frequency was implemented in 94.2% and 89%, respectively (p = 0.412). No predictors for the implementation of the guidelines were identified. Risk factors for becoming untraceable were none or lower number of heart surgeries, health insurance issues, and nonwhite ethnicity. In conclusion, a significant number of adults continue to be cared for by pediatric cardiologists, indicating that transfer to adult-oriented care was not standard practice. Frequency of follow-up for most patients was in line with the ACC/AHA 2008 guidelines. A considerable proportion of young adults were untraceable in the system, which makes them vulnerable for discontinuation of care. Copyright © 2015 Elsevier Inc. All rights reserved.

Fatigue in older adults with stable heart failure.

PubMed

Stephen, Sharon A

2008-01-01

The purpose of this study was to describe fatigue and the relationships among fatigue intensity, self-reported functional status, and quality of life in older adults with stable heart failure. A descriptive, correlational design was used to collect quantitative data with reliable and valid instruments. Fifty-three eligible volunteers completed a questionnaire during an interview. Those with recent changes in their medical regimen, other fatigue-inducing illnesses, and isolated diastolic dysfunction were excluded. Fatigue intensity (Profile of Mood States fatigue subscale) was associated with lower quality of life, perceived health, and satisfaction with life. Fatigue was common, and no relationship was found between fatigue intensity and self-reported functional status. Marital status was the only independent predictor of fatigue. In stable heart failure, fatigue is a persistent symptom. Clinicians need to ask patients about fatigue and assess the impact on quality of life. Self-reported functional status cannot serve as a proxy measure for fatigue.

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.

[Psychological aspects in adult congenital heart disease patients].

PubMed

Lahlou-Laforêt, Khadija

2013-03-01

Patients with congenital heart disease mostly owe their survival to a saving chirurgical intervention which confers them a survivor's identity. The relationships between parents and children are strongly influenced by these early events. The effort made by parents to allow a good quality of life to their child is often successful. However, difficulties to anticipate late complications are frequently observed in adolescents and young adult patients. In adulthood, these patients seem to discover suddenly their disease, its consequences and the necessity of long term follow-up. The coexistence of several changes, i.e adolescence, change of medical team, transfer of parental decision to the young adult own decision make this period a vulnerable way. An adapted multidisciplinary support aimed to a real transition may limit the risks of breaking off and better organize long term follow-up.

Comparison of the measurement of heart rate in adult free-range chickens (Gallus domesticus) by auscultation and electrocardiography.

PubMed

Smith, C F; Gavaghan, B J; McSweeney, D; Powell, V; Lisle, A

2014-12-01

To compare the heart rates of adult free-range chickens (Gallus domesticus) measured by auscultation with a stethoscope with those measured simultaneously using electrocardiography (ECG). With each bird in a standing position, estimation of the heart rate was performed by placing a mark on paper for every 4 beats for roosters and 8 beats for hens as detected by auscultation over 30 s, while simultaneous ECG was performed. Heart rates measured by auscultation showed a high correlation (r = 0.97) with those measured by ECG. There was a high correlation between the heart rates of adult free-range chickens measured by auscultation with a stethoscope and those measured simultaneously using ECG. © 2014 Australian Veterinary Association.

Advanced Echocardiography in Adult Zebrafish Reveals Delayed Recovery of Heart Function after Myocardial Cryoinjury

PubMed Central

Kossack, Mandy; Juergensen, Lonny; Fuchs, Dieter; Katus, Hugo A.; Hassel, David

2015-01-01

Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage. PMID:25853735

The care of adults with congenital heart disease across the globe: Current assessment and future perspective: A position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

PubMed

Webb, Gary; Mulder, Barbara J; Aboulhosn, Jamil; Daniels, Curt J; Elizari, Maria Amalia; Hong, Gu; Horlick, Eric; Landzberg, Michael J; Marelli, Ariane J; O'Donnell, Clare P; Oechslin, Erwin N; Pearson, Dorothy D; Pieper, Els P G; Saxena, Anita; Schwerzmann, Markus; Stout, Karen K; Warnes, Carole A; Khairy, Paul

2015-09-15

The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Improving Medication Knowledge among Older Adults with Heart Failure: A Patient-Centered Approach to Instruction Design

ERIC Educational Resources Information Center

Morrow, Daniel G.; Weiner, Michael; Young, James; Steinley, Douglas; Deer, Melissa; Murray, Michael D.

2005-01-01

Purpose: We investigated whether patient-centered instructions for chronic heart failure medications increase comprehension and memory for medication information in older adults diagnosed with chronic heart failure. Design and Methods: Patient-centered instructions for familiar and unfamiliar medications were compared with instructions for the…

Localization of cholinergic innervation and neurturin receptors in adult mouse heart and expression of the neurturin gene.

PubMed

Mabe, Abigail M; Hoard, Jennifer L; Duffourc, Michelle M; Hoover, Donald B

2006-10-01

Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the heart, but whether NRTN continues to function in the adult heart is unknown. We have therefore evaluated NRTN expression in adult mouse heart and the association of NRTN receptors with intracardiac cholinergic neurons and nerve fibers. Mapping the regional distribution and density of cholinergic nerves in mouse heart was an integral part of this goal. Analysis of RNA from adult C57BL/6 mouse hearts demonstrated NRTN expression in atrial and ventricular tissue. Virtually all neurons in the cardiac parasympathetic ganglia exhibited the cholinergic phenotype, and over 90% of these cells contained both components of the NRTN receptor, Ret tyrosine kinase and GDNF family receptor alpha2 (GFRalpha2). Cholinergic nerve fibers, identified by labeling for the high affinity choline transporter, were abundant in the sinus and atrioventricular nodes, ventricular conducting system, interatrial septum, and much of the right atrium, but less abundant in the left atrium. The right ventricular myocardium contained a low density of cholinergic nerves, which were sparse in other regions of the working ventricular myocardium. Some cholinergic nerves were also associated with coronary vessels. GFRalpha2 was present in most cholinergic nerve fibers and in Schwann cells and their processes throughout the heart. Some cholinergic nerve fibers, such as those in the sinus node, also exhibited Ret immunoreactivity. These findings provide the first detailed mapping of cholinergic nerves in mouse heart and suggest that the neurotrophic influence of NRTN on cardiac cholinergic innervation continues in mature animals.

The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

PubMed

Iaizzo, Paul A

2016-12-01

Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. To date, Visible ® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Visible Heart ® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

mAb C19 targets a novel surface marker for the isolation of human cardiac progenitor cells from human heart tissue and differentiated hESCs.

PubMed

Leung, Hau Wan; Moerkamp, Asja T; Padmanabhan, Jayanthi; Ng, Sze-Wai; Goumans, Marie-José; Choo, Andre

2015-05-01

Cardiac progenitor cells (CPCs) have been isolated from adult and developing hearts using an anti-mouse Sca-1 antibody. However, the absence of a human Sca-1 homologue has hampered the clinical application of the CPCs. Therefore, we generated novel monoclonal antibodies (mAbs) specifically raised against surface markers expressed by resident human CPCs. Here, we explored the suitability of one of these mAbs, mAb C19, for the identification, isolation and characterization of CPCs from fetal heart tissue and differentiating cultures of human embryonic stem cells (hESCs). Using whole-cell immunization, mAbs were raised against Sca-1+ CPCs and screened for reactivity to various CPC lines by flow cytometry. mAb C19 was found to be specific for Sca-1+ CPCs, with high cell surface binding capabilities. mAb C19 stained small stem-like cells in cardiac tissue sections. Moreover, during differentiation of hESCs towards cardiomyocytes, a transient population of cells with mAb C19 reactivity was identified and isolated using magnetic-activated cell sorting. Their cell fate was tracked and found to improve cardiomyocyte purity from hESC-derived cultures. mAb C19+ CPCs, from both hESC differentiation and fetal heart tissues, were maintained and expanded in culture, while retaining their CPC-like characteristics and their ability to further differentiate into cardiomyocytes by stimulation with TGFβ1. Finally, gene expression profiling of these mAb C19+ CPCs suggested a highly angiogenic nature, which was further validated by cell-based angiogenesis assays. mAb C19 is a new surface marker for the isolation of multipotent CPCs from both human heart tissues and differentiating hESCs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patient-reported outcomes in adults with congenital heart disease: Inter-country variation, standard of living and healthcare system factors.

PubMed

Moons, Philip; Kovacs, Adrienne H; Luyckx, Koen; Thomet, Corina; Budts, Werner; Enomoto, Junko; Sluman, Maayke A; Yang, Hsiao-Ling; Jackson, Jamie L; Khairy, Paul; Cook, Stephen C; Subramanyan, Raghavan; Alday, Luis; Eriksen, Katrine; Dellborg, Mikael; Berghammer, Malin; Johansson, Bengt; Mackie, Andrew S; Menahem, Samuel; Caruana, Maryanne; Veldtman, Gruschen; Soufi, Alexandra; Fernandes, Susan M; White, Kamila; Callus, Edward; Kutty, Shelby; Van Bulck, Liesbet; Apers, Silke

2018-01-15

Geographical differences in patient-reported outcomes (PROs) of adults with congenital heart disease (ConHD) have been observed, but are poorly understood. We aimed to: (1) investigate inter-country variation in PROs in adults with ConHD; (2) identify patient-related predictors of PROs; and (3) explore standard of living and healthcare system characteristics as predictors of PROs. Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS) was a cross-sectional, observational study, in which 4028 patients from 15 countries in 5 continents were enrolled. Self-report questionnaires were administered: patient-reported health (12-item Short Form Health Survey; EuroQOL-5D Visual Analog Scale); psychological functioning (Hospital Anxiety and Depression Scale); health behaviors (Health Behavior Scale-Congenital Heart Disease) and quality of life (Linear Analog Scale for quality of life; Satisfaction With Life Scale). A composite PRO score was calculated. Standard of living was expressed as Gross Domestic Product per capita and Human Development Index. Healthcare systems were operationalized as the total health expenditure per capita and the overall health system performance. Substantial inter-country variation in PROs was observed, with Switzerland having the highest composite PRO score (81.0) and India the lowest (71.3). Functional class, age, and unemployment status were patient-related factors that independently and consistently predicted PROs. Standard of living and healthcare system characteristics predicted PROs above and beyond patient characteristics. This international collaboration allowed us to determine that PROs in ConHD vary as a function of patient-related factors as well as the countries in which patients live. Copyright © 2017 Elsevier B.V. All rights reserved.

Knowledge of heart attack and stroke symptomology: a cross-sectional comparison of rural and non-rural US adults

PubMed Central

2012-01-01

Background Understanding the signs and symptoms of heart attacks and strokes are important not only in saving lives, but also in preserving quality of life. Findings from recent research have yielded that the prevalence of cardiovascular disease risk factors are higher in rural populations, suggesting that adults living in rural locales may be at higher risk for heart attack and/or stroke. Knowledge of heart attack and stroke symptomology as well as calling 911 for a suspected heart attack or stroke are essential first steps in seeking care. This study sought to examine the knowledge of heart attack and stroke symptoms among rural adults in comparison to non-rural adults living in the U.S. Methods Using multivariate techniques, a cross-sectional analysis of an amalgamated multi-year Behavioral Risk Factor Surveillance Survey (BRFSS) database was performed. The dependent variable for this analysis was low heart attack and stroke knowledge score. The covariates for the analysis were: age, sex, race/ethnicity, annual household income, attained education, health insurance status, having a health care provider (HCP), timing of last routine medical check-up, medical care deferment because of cost, self-defined health status and geographic locale. Results The weighted n for this study overall was 103,262,115 U.S. adults > =18 years of age. Approximately 22.0% of these respondents were U.S. adults living in rural locales. Logistic regression analysis revealed that those U.S. adults who had low composite heart attack and stroke knowledge scores were more likely to be rural (OR = 1.218 95%CI 1.216-1.219) rather than non-rural residents. Furthermore, those with low scores were more likely to be: male (OR = 1.353 95%CI 1.352-1.354), >65 years of age (OR = 1.369 95%CI 1.368-1.371), African American (OR = 1.892 95%CI 1.889-1.894), not educated beyond high school (OR = 1.400 955CI 1.399-1.402), uninsured (OR = 1.308 95%CI 1.3-6-1.310), without a HCP

High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

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

Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia

Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to lowmore » concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

Clinical implications of eicosapentaenoic acid/arachidonic acid ratio (EPA/AA) in adult patients with congenital heart disease.

PubMed

Kanoh, Miki; Inai, Kei; Shinohara, Tokuko; Tomimatsu, Hirofumi; Nakanishi, Toshio

2017-12-01

Recent studies showed that a low ratio between the levels of eicosapentaenoic acid and those of arachidonic acid (EPA/AA) is associated with higher incidence of coronary artery disease and poor prognosis of heart failure, arrhythmia, and cardiac sudden death. However, the clinical implications of EPA/AA in adult patients with congenital heart disease remain unclear. We aimed to assess the prognostic value of EPA/AA regarding cardiac events in adult patients with congenital heart disease. We measured the serum levels of eicosapentaenoic acid and arachidonic acid in 130 adult patients (median age, 31 years) stratified into two groups according to their EPA/AA (low, ≤0.22; high, >0.22). We prospectively analyzed the association between EPA/AA and incidence of cardiac events during a mean observation period of 15 months, expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI). In the subgroup of patients with biventricular circulation (2VC) (n = 76), we analyzed the same clinical endpoints. In our study population, EPA/AA was not associated with the incidence of arrhythmic events (HR, 1.52; 95% CI, 0.82-2.85; p = 0.19), but low EPA/AA was a predictor of heart failure hospitalization (HR, 2.83; 95% CI, 1.35-6.30; p < 0.01). Among patients with 2VC, an EPA/AA of ≤0.25 was associated with a significantly higher risk of arrhythmic events (HR, 2.55; 95% CI, 1.11-6.41; p = 0.03) and heart failure hospitalization (HR, 5.20; 95% CI, 1.78-18.1; p < 0.01). EPA/AA represents a useful predictor of cardiac events in adult patients with congenital heart disease.

The Miracle Baby Grows Up: Hypoplastic Left Heart Syndrome in the Adult.

PubMed

Lewis, Matthew; Rosenbaum, Marlon

2017-08-01

Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of the mitral valve, left ventricle, and aorta and is ultimately palliated with a single-ventricle repair. Universally fatal in infancy prior to the advent of modern surgical techniques, the majority of HLHS patients will now reach adulthood. However, despite improvements in early survival, the HLHS population continues to face significant morbidity and early mortality. This review delineates common sources of patient morbidity and highlights areas in need of additional research for this growing segment of the adult congenital heart disease population. It has become increasingly clear that palliated adult single ventricle patients, like those with HLHS, face significant life-long morbidity from elevated systemic venous pressures as a consequence of the Fontan procedure. Downstream organ dysfunction secondary to elevated Fontan pressures has the potential to significantly impact long-term management decisions, including strategies of organ allocation. Because of the presence of a morphologic systemic right ventricle, HLHS patients may be at even higher risk than other adult patients with a Fontan. Because the adult HLHS population continues to grow, recognition of common sources of patient morbidity and mortality is becoming increasingly important. A coordinated effort between patients and providers is necessary to address the many remaining areas of clinical uncertainty to help ensure continued improvement in patient prognosis and quality of life.

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

PubMed

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

2017-08-01

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

Localization of alpha 1-adrenoceptors in rat and human hearts by immunocytochemistry.

PubMed

Schulze, W; Fu, M L

1996-01-01

The localization of the alpha 1 adrenoceptors (alpha 1-AR) in the heart tissues from rat and human and in the cultured heart cells from neonatal rats was studied by indirect immunofluorescence and postembedding electronmicroscopical immuno-gold technique. With antipeptide antibodies directed against the second extracellular loop of the human alpha 1-AR (AS sequence 192-218), this receptor was found to be localized along the sarcolemma in both human and rat hearts. Similar localization sites were detected in cultivated rat neonatal cardiomyocytes. Beside the localization in cardiomyocytes, alpha 1-AR were identified in endothelial cells of capillaries and smooth muscle cells of coronary vessels, in neuronal endings, in mast cells of cultivated heart cells but not, or in less amount in fibroblasts. Interestingly, in the right atrium of rat heart the localization of alpha 1-AR was found to be near or on atrial natriuretic factor (ANF) granules, providing the basis for the alpha-adrenergic influence on ANF release. The immunocytochemical studies further confirm and complete the findings known by using autoradiographic binding studies with specific ligands.

Ventricular arrhythmias and sudden cardiac death in adults with congenital heart disease.

PubMed

Khairy, Paul

2016-11-01

Remarkable gains in survival have led to an unprecedented number of adults with congenital heart disease. Arrhythmias collectively comprise the most common complication encountered. Recognising the unique issues and challenges involved in managing arrhythmias in adults with congenital heart disease and the consequential decisions surrounding sudden death prevention, expert societies have proposed evidence-based recommendations. On the whole, acute ventricular arrhythmias are managed according to general cardiology guidelines, while taking into consideration congenital heart disease-specific issues, such as positioning of patches or paddles according to location of the heart. Implantable cardioverter-defibrillators (ICDs) are indicated for secondary prevention in patients with sustained ventricular tachycardia or resuscitated cardiac arrest in the absence of a reversible cause. Pharmacological therapy and catheter ablation can be effective in reducing recurrent ICD shocks. Risk-benefit assessment for primary prevention ICDs is a major challenge. Although a clearer picture has emerged of the high-risk patient with tetralogy of Fallot, ICD indications for those with systemic right ventricles or univentricular hearts remain contentious. Challenges to ICD implantation include obstructed veins, conduits and baffles, atrioventricular valve disease and intracardiac shunts. In selected patients, customised systems with epicardial and/or subcutaneous coils may represent a viable solution. Alternatively, the subcutaneous ICD is an attractive option for patients in whom transvenous access is not feasible or desirable and in whom bradycardia and antitachycardia pacing features are not essential. Continued advances in risk stratification and device technologies carry the potential to further improve efficacy and safety outcomes in this growing population of patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Air Quality Awareness Among U.S. Adults With Respiratory and Heart Disease.

PubMed

Mirabelli, Maria C; Boehmer, Tegan K; Damon, Scott A; Sircar, Kanta D; Wall, Hilary K; Yip, Fuyuen Y; Zahran, Hatice S; Garbe, Paul L

2018-05-01

Poor air quality affects respiratory and cardiovascular health. Information about health risks associated with outdoor air quality is communicated to the public using air quality alerts. This study was conducted to assess associations of existing respiratory and heart disease with three aspects of air quality awareness: awareness of air quality alerts, discussing with a health professional strategies to reduce air pollution exposure, and avoiding busy roads to reduce air pollution exposure when walking, biking, or exercising outdoors. During 2014-2016, a total of 12,599 U.S. adults participated in summer waves of the ConsumerStyles surveys and self-reported asthma, emphysema/chronic obstructive pulmonary disease, heart disease, and each aspect of air quality awareness. In 2017, associations between each health condition and air quality awareness were estimated using log binomial and multinomial regression. Overall, 49% of respondents were aware of air quality alerts, 3% discussed with a health professional strategies to reduce air pollution exposure, and 27% always/usually avoided busy roads to reduce air pollution exposure. Asthma was associated with increased prevalence of awareness of air quality alerts (prevalence ratio=1.11, 95% CI=1.04, 1.20), discussing with a health professional (prevalence ratio=4.88, 95% CI=3.74, 6.37), and always/usually avoiding busy roads to reduce air pollution exposure (prevalence ratio=1.13, 95% CI=1.01, 1.27). Heart disease was not associated with air quality awareness. Existing respiratory disease, but not heart disease, was associated with increased air quality awareness. These findings reveal important opportunities to raise awareness of air quality alerts and behavior changes aimed at reducing air pollution exposure among adults at risk of exacerbating respiratory and heart diseases. Published by Elsevier Inc.

Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

PubMed Central

Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

2017-01-01

Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

Association between resting heart rate and arterial stiffness in Korean adults.

PubMed

Park, Byoung-Jin; Lee, Hye-Ree; Shim, Jae-Yong; Lee, Jung-Hyun; Jung, Dong-Hyuk; Lee, Yong-Jae

2010-04-01

Higher resting heart rate, a simple and useful indicator of autonomic balance and metabolic rate, has emerged as an independent predictor for atherosclerotic cardiovascular disease. To determine the association between resting heart rate and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV). We examined the association between resting heart rate and baPWV in 641 Korean adults (366 men, 275 women) in a health examination program. A high baPWV was defined as greater than 1450 cm/s (>75th percentile). The odds ratios for high baPWVs were calculated using multivariable logistic regression analysis after adjusting for confounding variables across heart rate quartiles (Q1or=69 beats/min). Age-adjusted baPWV mean values increased gradually with heart rate quartile (Q1=1281, Q2=1285, Q3=1354, Q4=1416 cm/s). The odds ratios (95% confidence intervals) for high baPWVs in each heart rate quartile were 1.00, 1.28 (0.57-2.86), 2.63 (1.20-5.79) and 3.66 (1.66-8.05), respectively, after adjusting for age, sex, smoking status, alcohol intake, exercise, body mass index, hypertension medication, diabetes medication, hyperlipidaemia medication, mean arterial blood pressure, fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, white blood cell count, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase and uric acid. These findings indicate that a higher resting heart rate is independently associated with arterial stiffness. Accordingly, early detection of increased resting heart rate is important for preservation of arterial function and assessment of cardiovascular risk. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Overweight Status, Obesity, and Risk Factors for Coronary Heart Disease in Adults with Intellectual Disability

ERIC Educational Resources Information Center

Henderson, C. Michael; Robinson, Laura M.; Davidson, Philip W.; Haveman, Meindert; Janicki, Matthew P.; Albertini, Giorgio

2008-01-01

Research indicates that adults with intellectual disabilities (ID) have high rates of overweight status/obesity (OSO). OSO is associated with several important risk factors for coronary heart disease (CHD). This study focused on assessing whether such risk factors are being identified in adults with ID who are receiving their healthcare in…

Heart research advances using database search engines, Human Protein Atlas and the Sydney Heart Bank.

PubMed

Li, Amy; Estigoy, Colleen; Raftery, Mark; Cameron, Darryl; Odeberg, Jacob; Pontén, Fredrik; Lal, Sean; Dos Remedios, Cristobal G

2013-10-01

This Methodological Review is intended as a guide for research students who may have just discovered a human "novel" cardiac protein, but it may also help hard-pressed reviewers of journal submissions on a "novel" protein reported in an animal model of human heart failure. Whether you are an expert or not, you may know little or nothing about this particular protein of interest. In this review we provide a strategic guide on how to proceed. We ask: How do you discover what has been published (even in an abstract or research report) about this protein? Everyone knows how to undertake literature searches using PubMed and Medline but these are usually encyclopaedic, often producing long lists of papers, most of which are either irrelevant or only vaguely relevant to your query. Relatively few will be aware of more advanced search engines such as Google Scholar and even fewer will know about Quertle. Next, we provide a strategy for discovering if your "novel" protein is expressed in the normal, healthy human heart, and if it is, we show you how to investigate its subcellular location. This can usually be achieved by visiting the website "Human Protein Atlas" without doing a single experiment. Finally, we provide a pathway to discovering if your protein of interest changes its expression level with heart failure/disease or with ageing. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Regenerating new heart with stem cells

PubMed Central

Anversa, Piero; Kajstura, Jan; Rota, Marcello; Leri, Annarosa

2013-01-01

This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin. PMID:23281411

A Simple Dissection Method for the Conduction System of the Human Heart

ERIC Educational Resources Information Center

Yanagawa, Nariaki; Nakajima, Yuji

2009-01-01

A simple dissection guide for the conduction system of the human heart is shown. The atrioventricular (AV) node, AV bundle, and right bundle branch were identified in a formaldehyde-fixed human heart. The sinu-atrial (SA) node could not be found, but the region in which SA node was contained was identified using the SA nodal artery. Gross…

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

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

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

2006-07-12

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

Illness Identity: A Novel Predictor for Healthcare Use in Adults With Congenital Heart Disease.

PubMed

Van Bulck, Liesbet; Goossens, Eva; Luyckx, Koen; Oris, Leen; Apers, Silke; Moons, Philip

2018-05-22

To optimize healthcare use of adults with congenital heart disease, all important predictors of healthcare utilization should be identified. Clinical and psychological characteristics (eg, age and depression) have been found to be associated with healthcare use. However, the concept of illness identity, which assesses the degree to which congenital heart disease is integrated into one's identity, has not yet been investigated in association with healthcare use. Hence, the purpose of the study is to examine the predictive value of illness identity for healthcare use. In this ambispective analytical observational cohort study, 216 adults with congenital heart disease were included. The self-reported Illness Identity Questionnaire was used to assess illness identity states: engulfment, rejection, acceptance, and enrichment. After 1 year, self-reported healthcare use for congenital heart disease or other reasons over the past 6 months was assessed including hospitalizations; visits to general practitioner; visits to medical specialists; and emergency room visits. Binary logistic and negative binomial regression analyses were conducted, adjusting for age, sex, disease complexity, and depressive and anxious symptoms. The more profoundly the heart defect dominated one's identity (ie, engulfment), the more likely this person was to be hospitalized (odds ratio=3.76; 95% confidence interval=1.43-9.86), to visit a medical specialist (odds ratio=2.32; 95% confidence interval=1.35-4.00) or a general practitioner (odds ratio=1.78; 95% confidence interval=1.01-3.17), because of their heart defect. Illness identity, more specifically engulfment, has a unique predictive value for the occurrence of healthcare encounters. This association deserves further investigation, in which the directionality of effects and the contribution of illness identity in terms of preventing inappropriate healthcare use should be determined. © 2018 The Authors. Published on behalf of the American

Exercise for Preventing Hospitalization and Readmission in Adults with Congestive Heart Failure.

PubMed

Aronow, Wilbert S; Shamliyan, Tatyana A

2018-05-04

We critically appraised all available evidence regarding exercise interventions for improving patient survival and reducing hospital admissions in adults with chronic heart failure (HF). We searched 4 databases up to April 2018 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group approach. We reviewed 7 meta-analyses and the publications of 48 randomized, controlled trials (RCT). In HF with reduced ejection fraction, low-quality evidence suggests that exercise prevents all-cause hospitalizations (RR 0.77; 95% CI 0.63;0.93; 1328 patients in 15 RCTs) and hospitalizations due to HF (RR 0.57; 95% CI 0.37;0.88; 1073 patients in 13 RCTs) and improves quality of life (standardized mean difference [SMD] -0.37; 95% CI -0.60;-0.14; 1270 patients in 25 RCTs) but has no effect on mortality. In HF with preserved ejection fraction, low-quality evidence suggests that exercise improves peak oxygen uptake (mean difference [MD] 2.36; 95% CI 1.16;3.57; 171 patients in 3 RCTs) and quality of life (MD -4.65; 95% CI -8.46;-0.83; 203 patients in 4 RCTs). In patients after heart transplantation, low-quality evidence suggests that exercise improves peak oxygen uptake (SMD 0.68; 95% CI 0.43;0.93; 284 patients in 9 RCTs) but does not improve quality of life. In order to reduce hospitalization and improve quality of life for adults with HF and reduced ejection fraction, clinicians should recommend exercise interventions. For adults with HF and preserved ejection fraction and in those undergoing heart transplantation, clinicians may recommend exercise interventions in order to improve peak oxygen uptake.

High Contrast Ultrafast Imaging of the Human Heart

PubMed Central

Papadacci, Clement; Pernot, Mathieu; Couade, Mathieu; Fink, Mathias; Tanter, Mickael

2014-01-01

Non-invasive ultrafast imaging for human cardiac applications is a big challenge to image intrinsic waves such as electromechanical waves or remotely induced shear waves in elastography imaging techniques. In this paper we propose to perform ultrafast imaging of the heart with adapted sector size by using diverging waves emitted from a classical transthoracic cardiac phased array probe. As in ultrafast imaging with plane wave coherent compounding, diverging waves can be summed coherently to obtain high-quality images of the entire heart at high frame rate in a full field-of-view. To image shear waves propagation at high SNR, the field-of-view can be adapted by changing the angular aperture of the transmitted wave. Backscattered echoes from successive circular wave acquisitions are coherently summed at every location in the image to improve the image quality while maintaining very high frame rates. The transmitted diverging waves, angular apertures and subapertures size are tested in simulation and ultrafast coherent compounding is implemented on a commercial scanner. The improvement of the imaging quality is quantified in phantom and in vivo on human heart. Imaging shear wave propagation at 2500 frame/s using 5 diverging waves provides a strong increase of the Signal to noise ratio of the tissue velocity estimates while maintaining a high frame rate. Finally, ultrafast imaging with a 1 to 5 diverging waves is used to image the human heart at a frame rate of 900 frames/s over an entire cardiac cycle. Thanks to spatial coherent compounding, a strong improvement of imaging quality is obtained with a small number of transmitted diverging waves and a high frame rate, which allows imaging the propagation of electromechanical and shear waves with good image quality. PMID:24474135

Imaging of congenital heart disease in adults: choice of modalities.

PubMed

Orwat, Stefan; Diller, Gerhard-Paul; Baumgartner, Helmut

2014-01-01

Major advances in noninvasive imaging of adult congenital heart disease have been accomplished. These tools play now a key role in comprehensive diagnostic work-up, decision for intervention, evaluation for the suitability of specific therapeutic options, monitoring of interventions and regular follow-up. Besides echocardiography, magnetic resonance (CMR) and computed tomography (CT) have gained particular importance. The choice of imaging modality has thus become a critical issue. This review summarizes strengths and limitations of the different imaging modalities and how they may be used in a complementary fashion. Echocardiography obviously remains the workhorse of imaging routinely used in all patients. However, in complex disease and after surgery echocardiography alone frequently remains insufficient. CMR is particularly useful in this setting and allows reproducible and accurate quantification of ventricular function and comprehensive assessment of cardiac anatomy, aorta, pulmonary arteries and venous return including complex flow measurements. CT is preferred when CMR is contraindicated, when superior spatial resolution is required or when "metallic" artefacts limit CMR imaging. In conclusion, the use of currently available imaging modalities in adult congenital heart disease needs to be complementary. Echocardiography remains the basis tool, CMR and CT should be added considering specific open questions and the ability to answer them, availability and economic issues.

Cell Therapy Trials in Congenital Heart Disease.

PubMed

Oh, Hidemasa

2017-04-14

Dramatic evolution in medical and catheter interventions and complex surgeries to treat children with congenital heart disease (CHD) has led to a growing number of patients with a multitude of long-term complications associated with morbidity and mortality. Heart failure in patients with hypoplastic left heart syndrome predicated by functional single ventricle lesions is associated with an increase in CHD prevalence and remains a significant challenge. Pathophysiological mechanisms contributing to the progression of CHD, including single ventricle lesions and dilated cardiomyopathy, and adult heart disease may inevitably differ. Although therapeutic options for advanced cardiac failure are restricted to heart transplantation or mechanical circulatory support, there is a strong impetus to develop novel therapeutic strategies. As lower vertebrates, such as the newt and zebrafish, have a remarkable ability to replace lost cardiac tissue, this intrinsic self-repair machinery at the early postnatal stage in mice was confirmed by partial ventricular resection. Although the underlying mechanistic insights might differ among the species, mammalian heart regeneration occurs even in humans, with the highest degree occurring in early childhood and gradually declining with age in adulthood, suggesting the advantage of stem cell therapy to ameliorate ventricular dysfunction in patients with CHD. Although effective clinical translation by a variety of stem cells in adult heart disease remains inconclusive with respect to the improvement of cardiac function, case reports and clinical trials based on stem cell therapies in patients with CHD may be invaluable for the next stage of therapeutic development. Dissecting the differential mechanisms underlying progressive ventricular dysfunction in children and adults may lead us to identify a novel regenerative therapy. Future regenerative technologies to treat patients with CHD are exciting prospects for heart regeneration in general

The human subject: an integrative animal model for 21st century heart failure research

PubMed Central

Chandrasekera, P Charukeshi; Pippin, John J

2015-01-01

Heart failure remains a leading cause of death and it is a major cause of morbidity and mortality affecting tens of millions of people worldwide. Despite decades of extensive research conducted at enormous expense, only a handful of interventions have significantly impacted survival in heart failure. Even the most widely prescribed treatments act primarily to slow disease progression, do not provide sustained survival advantage, and have adverse side effects. Since mortality remains about 50% within five years of diagnosis, the need to increase our understanding of heart failure disease mechanisms and development of preventive and reparative therapies remains critical. Currently, the vast majority of basic science heart failure research is conducted using animal models ranging from fruit flies to primates; however, insights gleaned from decades of animal-based research efforts have not been proportional to research success in terms of deciphering human heart failure and developing effective therapeutics for human patients. Here we discuss the reasons for this translational discrepancy which can be equally attributed to the use of erroneous animal models and the lack of widespread use of human-based research methodologies and address why and how we must position our own species at center stage as the quintessential animal model for 21st century heart failure research. If the ultimate goal of the scientific community is to tackle the epidemic status of heart failure, the best way to achieve that goal is through prioritizing human-based, human-relevant research. PMID:26550463

CDC Vital Signs: Heart Age - Is Your Heart Older Than You?

MedlinePlus

... Digital Press Kit Read the MMWR Science Clips Heart Age Is Your Heart Older Than You? Language: ... that increase heart age. Problem US adults have hearts 7 years older than they should be. Though ...

Characteristics and outcomes of heart failure-related hospitalization in adults with congenital heart disease.

PubMed

Moussa, Nidhal Ben; Karsenty, Clement; Pontnau, Florence; Malekzadeh-Milani, Sophie; Boudjemline, Younes; Legendre, Antoine; Bonnet, Damien; Iserin, Laurence; Ladouceur, Magalie

2017-05-01

Heart failure (HF) is the main cause of death in adult congenital heart disease (ACHD). We aimed to characterize HF-related hospitalization of patients with ACHD, and to determine HF risk factors and prognosis in this population. We prospectively included 471 patients with ACHD admitted to our unit over 24 months. Clinical and biological data and HF management were recorded. Major cardiovascular events were recorded for ACHD with HF. HF was the main reason for hospitalization in 13% of cases (76/583 hospitalizations). Patients with HF were significantly older (median age 44±14 years vs. 37±15 years; P<0.01), with more complex congenital heart disease (P=0.04). In the multivariable analysis, pulmonary arterial hypertension (odds ratio [OR] 6.2, 95% confidence interval [CI] 3.5-10.7), history of HF (OR 9.8, 95% CI 5.7-16.8) and history of atrial arrhythmia (OR 3.6, 95% CI 2.2-5.9) were significant risk factors for HF-related admissions (P<0.001). The mean hospital stay of patients with HF was longer (12.2 vs. 6.9 days; P<0.01), and 25% of patients required intensive care. Overall, 11/55 (20%) patients with HF died, 10/55 (18%) were readmitted for HF, and 6/55 (11%) had heart transplantation during the median follow-up of 18 months (95% CI 14-20 months). The risk of cardiovascular events was 19-fold higher after HF-related hospitalization. HF is emerging as a leading cause of morbidity and mortality in the ACHD population. Earlier diagnosis and more active management are required to improve outcomes of HF in ACHD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Medication-related cognitive artifacts used by older adults with heart failure

PubMed Central

Mickelson, Robin S.; Willis, Matt; Holden, Richard J.

2015-01-01

Objective To use a human factors perspective to examine how older adult patients with heart failure use cognitive artifacts for medication management. Methods We performed a secondary analysis of data collected from 30 patients and 14 informal caregivers enrolled in a larger study of heart failure self-care. Data included photographs, observation notes, interviews, video recordings, medical record data, and surveys. These data were analyzed using an iterative content analysis. Results Findings revealed that medication management was complex, inseparable from other patient activities, distributed across people, time, and place, and complicated by knowledge gaps. We identified fifteen types of cognitive artifacts including medical devices, pillboxes, medication lists, and electronic personal health records used for: 1) measurement/evaluation; 2) tracking/communication; 3) organization/administration; and 4) information/sensemaking. These artifacts were characterized by fit and misfit with the patient’s sociotechnical system and demonstrated both advantages and disadvantages. We found that patients often modified or “finished the design” of existing artifacts and relied on “assemblages” of artifacts, routines, and actors to accomplish their self-care goals. Conclusions Cognitive artifacts are useful but sometimes are poorly designed or are not used optimally. If appropriately designed for usability and acceptance, paper-based and computer-based information technologies can improve medication management for individuals living with chronic illness. These technologies can be designed for use by patients, caregivers, and clinicians; should support collaboration and communication between these individuals; can be coupled with home-based and wearable sensor technology; and must fit their users’ needs, limitations, abilities, tasks, routines, and contexts of use. PMID:26855882

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

PubMed

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

2018-05-30

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

Human Fetal Heart Rate Dishabituation between Thirty and Thirty-Two Weeks Gestation.

ERIC Educational Resources Information Center

Sandman, Curt A.; Wadhwa, Pathik; Hetrick, William; Porto, Manuel; Peeke, Harmon V. S.

1997-01-01

Examined the ability of 32-week human fetuses to learn and recall information. Found a significant heart rate habituation pattern for a series of vibroacoustic stimuli. After a single novel stimulus, the heart rate to stimulus 1 reemerged. Uterine contractions were not related to presentation of the novel stimulus or change in heart rate after the…

Gerbode defect and multivalvular dysfunction: Complex complications in adult congenital heart disease.

PubMed

Ruivo, Catarina; Guardado, Joana; Montenegro Sá, Fernando; Saraiva, Fátima; Antunes, Alexandre; Correia, Joana; Morais, João

2017-07-01

We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted with acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic and severely incompetent aortic valve, a partial tear of the mitral valve cleft repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial shunt confirmed a direct Gerbode defect. The authors aim to discuss the diagnostic challenge of adult CHD, namely the key role of TEE on septal defects and valve regurgitations description. © 2017, Wiley Periodicals, Inc.

[The Relationships among Perceived Parental Bonding, Illness Perception, and Anxiety in Adult Patients with Congenital Heart Diseases].

PubMed

Shin, Nayeon; Jang, Youha; Kang, Younhee

2017-04-01

The purposes of this study were to identify the relationships among perceived parental bonding, illness perception, and anxiety and to determine the influences of perceived parental bonding and illness perception on anxiety in adult patients with congenital heart diseases. In this study a descriptive correlational design with survey method was utilized. The participants were 143 adult patients with congenital heart disease being cared for in the cardiology out-patient clinic of A medical center. Data were collected using the Parental Bonding Instrument, Illness Perception Questionnaire Revised Scale, and Cardiac Anxiety Questionnaire Scale. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation analysis, and hierarchial regression analyses. There showed significant positive relationships of anxiety with maternal overprotection, consequences, and personal control respectively. Among predictors, maternal overprotection (β=.45), consequence (β=.26), and personal control (β=-.03) had statistically significant influence on anxiety. Nursing interventions to decrease maternal overprotection and negative consequence, and to enhance personal control are essential to decrease the anxiety of adult patients with congenital heart diseases. © 2017 Korean Society of Nursing Science

Cardiomyocyte-Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans.

PubMed

Sharifi-Sanjani, Maryam; Oyster, Nicholas M; Tichy, Elisia D; Bedi, Kenneth C; Harel, Ofer; Margulies, Kenneth B; Mourkioti, Foteini

2017-09-07

Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex. We studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single-cell resolution. In this study, total of 63 human left ventricular samples, including 37 diseased and 26 nonfailing donor hearts, were stained for telomeres in combination with cardiomyocyte- or α-smooth muscle cell-specific markers, cardiac troponin T, and smooth muscle actin, respectively, and assessed for telomere length. Patients with heart failure demonstrate shorter cardiomyocyte telomeres compared with nonfailing donors, which is specific only to cardiomyocytes within diseased human hearts and is associated with cardiomyocyte DNA damage. Our data further reveal that hypertrophic hearts with reduced ejection fraction exhibit the shortest telomeres. In contrast to other reported cell types, no difference in cardiomyocyte telomere length is evident with age. However, under the disease state, telomere attrition manifests in both young and older patients with cardiac hypertrophy. Finally, we demonstrate that cardiomyocyte-telomere length is better sustained in women than men under diseased conditions. This study provides the first evidence of cardiomyocyte-specific telomere shortening in heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Awareness of heart attack symptoms among US adults in 2007, and changes in awareness from 2001 to 2007.

PubMed

Fang, Jing; Gillespie, Cathleen; Keenan, Nora L; Greenlund, Kurt J

2011-05-01

Timely access to emergency care, prompt receipt of advanced treatment and survival from heart attack is dependent on both the early recognition of heart attack symptoms, by both victims and bystanders, and by immediately calling the emergency services. The objective of this study is to measure the awareness of heart attack symptoms and the emergency response among US adults. We analyzed data from the Behavioral Risk Factor Surveillance System's module on heart attack and stroke, which was conducted in 17 states/territories in 2001 and 12 states/territories in 2007. The module included five questions related to heart attack symptoms, one decoy question and one question regarding the first action to take if someone is having a heart attack. Age-adjusted prevalence of awareness was estimated, and odds ratios were calculated. Differences between 2001 and 2007 were assessed for five states that used the module in both years. In 2007, among 76,864 adults, awareness of individual heart attack symptoms ranged from 49% (pain in jaw, neck or back) to 92% (chest pain). Although 97% of adults recognized at least one symptom, only 10.7% recognized all five symptoms, knew that 'sudden trouble seeing in one or both eyes' was not a symptom of heart attack and recognized the need to call the emergency services. This estimate varied significantly by age, sex, race/ethnicity and level of education. The estimate was significantly higher for women (12.2%) than men (7.7%), White (11.6%) than Black (5.7%) or Hispanic people (4.5%), those with a higher level of education (13.5%) than lower educational level (4.5%) and for those with coronary heart disease (16.2%) than without the disease (9.5%). Comparison of awareness between 2001 (the referent) and 2007, in five states, revealed that awareness of all symptoms and calling the emergency services, were 9.7 and 10.3% for 2001 and 2007, respectively (p < 0.01). Compared to 2001, the odds ratio of awareness in 2007 was 1.08 (95% CI: 0

Cardiopulmonary Resuscitation in Adults and Children With Mechanical Circulatory Support: A Scientific Statement From the American Heart Association.

PubMed

Peberdy, Mary Ann; Gluck, Jason A; Ornato, Joseph P; Bermudez, Christian A; Griffin, Russell E; Kasirajan, Vigneshwar; Kerber, Richard E; Lewis, Eldrin F; Link, Mark S; Miller, Corinne; Teuteberg, Jeffrey J; Thiagarajan, Ravi; Weiss, Robert M; O'Neil, Brian

2017-06-13

Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients. © 2017 American Heart Association, Inc.

Left atrial appendages from adult hearts contain a reservoir of diverse cardiac progenitor cells.

PubMed

Leinonen, Jussi V; Emanuelov, Avishag K; Platt, Yardanna; Helman, Yaron; Feinberg, Yael; Lotan, Chaim; Beeri, Ronen

2013-01-01

There is strong evidence supporting the claim that endogenous cardiac progenitor cells (CPCs) are key players in cardiac regeneration, but the anatomic source and phenotype of the master cardiac progenitors remains uncertain. Our aim was to investigate the different cardiac stem cell populations in the left atrial appendage (LAA) and their fates. We investigated the CPC content and profile of adult murine LAAs using immunohistochemistry and flow cytometry. We demonstrate that the LAA contains a large number of CPCs relative to other areas of the heart, representing over 20% of the total cell number. We grew two distinct CPC populations from the LAA by varying the degree of proteolysis. These differed by their histological location, surface marker profiles and growth dynamics. Specifically, CD45(pos) cells grew with milder proteolysis, while CD45(neg) cells grew mainly with more intense proteolysis. Both cell types could be induced to differentiate into cells with cardiomyocyte markers and organelles, albeit by different protocols. Many CD45(pos) cells expressed CD45 initially and rapidly lost its expression while differentiating. Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts. Two different types of CPCs were isolated, differing in their epicardial-myocardial localization. Considering studies demonstrating layer-specific origins of different cardiac progenitor cells, our findings may shed light on possible pathways to study and utilize the diversity of endogenous progenitor cells in the adult heart.

The impact of obesity on early postoperative outcomes in adults with congenital heart disease.

PubMed

Zaidi, Ali N; Bauer, John A; Michalsky, Marc P; Olshove, Vincent; Boettner, Bethany; Phillips, Alistair; Cook, Stephen C

2011-01-01

As the prevalence of obesity continues to increase, it now includes the growing number of patients with congenital heart disease (CHD). This particular obese patient population may pose additional intraoperative as well as postoperative challenges that may contribute to poor outcomes. Our aims were to determine the influence of obesity on morbidity and mortality in adults with CHD undergoing surgical repair at a free standing children's hospital. A retrospective analysis of adult (≥18 years) CHD surgery cases from 2002 to 2008 was performed. Congenital heart lesions were defined as mild, moderate, or complex. Patients were categorized by body mass index (BMI): underweight (BMI < 20 kg/m(2)), normal (BMI 20-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)), and obese (BMI ≥ 30 kg/m(2)). Demographics, incidence of mortality, or specific morbidities were statistically compared using Fisher's exact test and analyses of variance (anovas). In this population (n = 165), overweight (29%) and obese (22%) patients were prevalent. Hypertension (HTN) and pre-HTN were more prevalent in obese and overweight patients. Postoperative renal dysfunction was observed in obese patients with complex CHD (P = .04). Mortality was not different among groups. Obesity is becoming increasingly common among adults with CHD. Despite marginal evidence of postoperative renal complications in obese patients with CHD of severe complexity, the overall presence of obesity did not influence mortality or short term postoperative morbidities. © 2011 Copyright the Authors. Congenital Heart Disease © 2011 Wiley Periodicals, Inc.

Visualization of human heart conduction system by means of fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Venius, Jonas; Bagdonas, Saulius; Žurauskas, Edvardas; Rotomskis, Ricardas

2011-10-01

The conduction system of the heart is a specific muscular tissue, where a heartbeat signal originates and initiates the depolarization of the ventricles. The muscular origin makes it complicated to distinguish the conduction system from the surrounding tissues. A surgical intervention can lead to the accidental harm of the conduction system, which may eventually result in a dangerous obstruction of the heart functionality. Therefore, there is an immense necessity for developing a helpful method to visualize the conduction system during the operation time. The specimens for the spectroscopic studies were taken from nine diverse human hearts. The localization of distinct types of the tissue was preliminary marked by the pathologist and approved histologically after the spectral measurements. Variations in intensity, as well as in shape, were detected in autofluorescence spectra of different heart tissues. The most distinct differences were observed between the heart conduction system and the surrounding tissues under 330 and 380 nm excitation. The spectral region around 460 nm appeared to be the most suitable for an unambiguous differentiation of the human conduction system avoiding the absorption peak of blood. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, was also demonstrated.

A binational registry of adults with pulmonary arterial hypertension complicating congenital heart disease.

PubMed

Strange, G; Rose, M; Kermeen, F; O'Donnell, C; Keogh, A; Kotlyar, E; Grigg, L; Bullock, A; Disney, P; Dwyer, N; Whitford, H; Tanous, D; Frampton, C; Weintraub, R; Celermajer, D S

2015-09-01

The management of children with congenital heart disease (CHD) has improved over recent decades and several patients surviving with CHD into adulthood are increasing. In developed countries, there are now as many adults as there are children living with CHD. Pulmonary arterial hypertension (PAH) occurs in ∼ 5% of patients with CHD. We aimed to understand the characteristics and outcomes of this emerging population. We collected data retrospectively and prospectively from 12 contributing centres across Australia and New Zealand (2010-2013). Patients were included if they had been diagnosed with PAH and CHD and had been seen once in an adult centre after 1 January 2000. Of 360 patients with CHD-PAH, 60% were female and 90% were New York Heart Association functional class II or III at the time of adult diagnosis of PAH. Mean age at diagnosis of PAH in adulthood was 31.2 ± 14 years, and on average, patients were diagnosed with PAH 6 years after symptom onset. All-cause mortality was 12% at 5 years, 21% at 10 years and 31% at 15 years. One hundred and six patients (30%) experienced 247 hospitalisations during 2936 patient years of follow up. Eighty-nine per cent of patients were prescribed PAH specific therapy (mean exposure of 4.0 years). Adults with PAH and CHD often have this diagnosis made after significant delay, and have substantial medium-term morbidity and mortality. This suggests a need for children transitioning to adult care with CHD to be closely monitored for this complication. © 2015 Royal Australasian College of Physicians.

High-Resolution Tissue Doppler Imaging of the Zebrafish Heart During Its Regeneration

PubMed Central

Su, Ta-Han; Shih, Cho-Chiang

2015-01-01

Abstract The human heart cannot regenerate after injury, whereas the adult zebrafish can fully regenerate its heart even after 20% of the ventricle is amputated. Many studies have begun to reveal the cellular and molecular mechanisms underlying this regenerative process, which have exciting implications for human cardiac diseases. However, the dynamic functions of the zebrafish heart during regeneration are not yet understood. This study established a high-resolution echocardiography for tissue Doppler imaging (TDI) of the zebrafish heart to explore the cardiac functions during different regeneration phases. Experiments were performed on AB-line adult zebrafish (n=40) in which 15% of the ventricle was surgically removed. An 80-MHz ultrasound TDI based on color M-mode imaging technology was employed. The cardiac flow velocities and patterns from both the ventricular chamber and myocardium were measured at different regeneration phases relative to the day of amputation. The peak velocities of early diastolic inflow, early diastolic myocardial motion, late diastolic myocardial motion, early diastolic deceleration slope, and heart rate were increased at 3 days after the myocardium amputation, but these parameters gradually returned to close to their baseline values for the normal heart at 7 days after amputation. The peak velocities of late diastolic inflow, ventricular systolic outflow, and systolic myocardial motion did not significantly differ during the heart regeneration. PMID:25517185

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

PubMed

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

2017-02-01

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

General anesthesia suppresses normal heart rate variability in humans

NASA Astrophysics Data System (ADS)

Matchett, Gerald; Wood, Philip

2014-06-01

The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

Transmural heterogeneity of cellular level power output is reduced in human heart failure.

PubMed

Haynes, Premi; Nava, Kristofer E; Lawson, Benjamin A; Chung, Charles S; Mitov, Mihail I; Campbell, Stuart G; Stromberg, Arnold J; Sadayappan, Sakthivel; Bonnell, Mark R; Hoopes, Charles W; Campbell, Kenneth S

2014-07-01

Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces transmural region-specific changes in contractile function. Permeabilized samples were prepared from the sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in vitro index of systolic function, was higher in non-failing mid-myocardial samples (0.59±0.06μWmg(-1)) than in samples from the sub-epicardium (p=0.021) and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also produced more isometric force (14.3±1.33kNm(-2)) than samples from the sub-epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid-myocardial tissue from failing hearts contained more collagen than matched sub-epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was correlated with the relative content of actin and troponin I, and was also statistically linked to the relative content and phosphorylation of desmin and myosin light chain-1. Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Baseline heart rate, sensation seeking, and aggression in young adult women: a two-sample examination.

PubMed

Wilson, Laura C; Scarpa, Angela

2013-01-01

Although substantial literature discusses sensation seeking as playing a role in the relationship between baseline heart rate and aggression, few published studies have tested the relationships among these variables. Furthermore, most prior studies have focused on risk factors of aggression in men and have largely ignored this issue in women. Two samples (n = 104; n = 99) of young adult women completed measures of resting heart rate, sensation seeking, and aggression. Across the two samples of females there was no evidence for the relationships of baseline heart rate with sensation seeking or with aggression that has been consistently shown in males. Boredom susceptibility and disinhibition subscales of sensation seeking were consistently significantly correlated with aggression. The lack of significance and the small effect sizes indicate that other mechanisms are also at work in affecting aggression in young adult women. Finally, it is important to consider the type of sensation seeking in relation to aggression, as only boredom susceptibility and disinhibition were consistently replicated across samples. © 2013 Wiley Periodicals, Inc.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

PubMed

Wilson, K S; Baily, J; Tucker, C S; Matrone, G; Vass, S; Moran, C; Chapman, K E; Mullins, J J; Kenyon, C; Hadoke, P W F; Denvir, M A

2015-10-15

Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart

PubMed Central

Wilson, K.S.; Baily, J.; Tucker, C.S.; Matrone, G.; Vass, S.; Moran, C.; Chapman, K.E.; Mullins, J.J.; Kenyon, C.; Hadoke, P.W.F.; Denvir, M.A.

2015-01-01

Background Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. PMID:26219824

Systems Approach to Understanding Electromechanical Activity in the Human Heart

PubMed Central

Rudy, Yoram; Ackerman, Michael J.; Bers, Donald M.; Clancy, Colleen E.; Houser, Steven R.; London, Barry; McCulloch, Andrew D.; Przywara, Dennis A.; Rasmusson, Randall L.; Solaro, R. John; Trayanova, Natalia A.; Van Wagoner, David R.; Varró, András; Weiss, James N.; Lathrop, David A.

2010-01-01

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation–contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm. PMID:18779456

Heart rate and suicide: findings from two cohorts of 533 000 Taiwanese and 75 000 Norwegian adults.

PubMed

Chang, S-S; Bjørngaard, J H; Tsai, M K; Bjerkeset, O; Wen, C P; Yip, P S F; Tsao, C K; Gunnell, D

2016-04-01

To investigate the association of resting heart rate with suicide in two large cohorts. The MJ cohort (Taiwan) included 532 932 adults from a health check-up programme (1994-2008). The HUNT cohort (Norway) included 74 977 adults in the Nord-Trøndelag County study (1984-1986), followed up to 2004. In both cohorts heart rate was measured at baseline, and suicide was ascertained through linkage to cause-of-death registers. Risk of suicide was estimated using Cox proportional hazards models. There were 569 and 188 suicides (average follow-up period of 8.1 and 16.9 years) in the MJ and HUNT cohorts respectively. Sex- and age-adjusted hazard ratio for every 10 beat increase in heart rate per minute was 1.08 (95% Confidence Interval 1.00-1.16) and 1.24 (1.12-1.38) in the MJ and HUNT cohorts, respectively. In the MJ cohort this association was confined to individuals with a history of heart diseases vs. those without such a history (P for interaction = 0.008). In the HUNT cohort the association did not differ by history of heart diseases and was robust to adjustment for health-related life style, medication use, and symptoms of anxiety and depression. Elevated resting heart rate may be a marker of increased suicide risk. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

FastStats: Heart Disease

MedlinePlus

... this? Submit What's this? Submit Button NCHS Home Heart Disease Recommend on Facebook Tweet Share Compartir Data are ... the U.S. Morbidity Number of adults with diagnosed heart disease: 28.1 million Percent of adults with diagnosed ...

Metabolic Syndrome and Short-Term Heart Rate Variability in Adults with Intellectual Disabilities

ERIC Educational Resources Information Center

Chang, Yaw-Wen; Lin, Jin-Ding; Chen, Wei-Liang; Yen, Chia-Feng; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Li-Wei

2012-01-01

Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV…

Optical mapping of Langendorff-perfused human hearts: establishing a model for the study of ventricular fibrillation in humans.

PubMed

Nanthakumar, Kumaraswamy; Jalife, José; Massé, Stéphane; Downar, Eugene; Pop, Mihaela; Asta, John; Ross, Heather; Rao, Vivek; Mironov, Sergey; Sevaptsidis, Elias; Rogers, Jack; Wright, Graham; Dhopeshwarkar, Rajesh

2007-07-01

Our objective was to establish a novel model for the study of ventricular fibrillation (VF) in humans. We adopted the established techniques of optical mapping to human ventricles for the first time to determine whether human VF is the result of wave breaks and singularity point formation and is maintained by high-frequency rotors and fibrillatory conduction. We describe the technique of acquiring optical signals in human hearts during VF, their characteristics, and the feasibility of possible analyses that could be performed to elucidate mechanisms of human VF. We used explanted hearts from five cardiomyopathic patients who underwent transplantation. The hearts were Langendorff perfused with Tyrode solution (95% O(2)-5% CO(2)), and the potentiometric dye di-4-ANEPPS was injected as a bolus into the coronary circulation. Fluorescence was excited at 531 +/- 20 nm with a 150-W halogen light source; the emission signal was long-pass filtered at 610 nm and recorded with a mapping camera. Fractional change of fluorescence varied between 2% and 12%. Average signal-to-noise ratio was 40 dB. The mean velocity of VF wave fronts was 0.25 +/- 0.04 m/s. Submillimetric spatial resolution (0.65-0.85 mm), activation mapping, and transformation of the data to phase-based analysis revealed reentrant, colliding, and fractionating wave fronts in human VF. On many occasions the VF wave fronts were as large as the entire vertical length (8 cm) of the mapping field, suggesting that there are a limited number of wave fronts on the human heart during VF. Phase transformation of the optical signals allowed the first demonstration ever of phase singularity point, wave breaks, and rotor formation in human VF. This method provides opportunities for potential analyses toward elucidation of the mechanisms of VF and defibrillation in humans.

Understanding age-based transition needs: Perspectives from adolescents and adults with congenital heart disease

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information ...

Minimal changes in heart rate of incubating American Oystercatchers (Haematopus palliatus) in response to human activity

USGS Publications Warehouse

Borneman, Tracy E.; Rose, Eli T.; Simons, Theodore R.

2014-01-01

An organism's heart rate is commonly used as an indicator of physiological stress due to environmental stimuli. We used heart rate to monitor the physiological response of American Oystercatchers (Haematopus palliatus) to human activity in their nesting environment. We placed artificial eggs with embedded microphones in 42 oystercatcher nests to record the heart rate of incubating oystercatchers continuously for up to 27 days. We used continuous video and audio recordings collected simultaneously at the nests to relate physiological response of birds (heart rate) to various types of human activity. We observed military and civilian aircraft, off-road vehicles, and pedestrians around nests. With the exception of high-speed, low-altitude military overflights, we found little evidence that oystercatcher heart rates were influenced by most types of human activity. The low-altitude flights were the only human activity to significantly increase average heart rates of incubating oystercatchers (12% above baseline). Although statistically significant, we do not consider the increase in heart rate during high-speed, low-altitude military overflights to be of biological significance. This noninvasive technique may be appropriate for other studies of stress in nesting birds.

Recent advancements in understanding endogenous heart regeneration—insights from adult zebrafish and neonatal mice

PubMed Central

Rubin, Nicole; Harrison, Michael R.; Krainock, Michael; Kim, Richard; Lien, Ching-Ling

2016-01-01

Enhancing the endogenous regenerative capacity of the mammalian heart is a promising strategy that can lead to potential treatment of injured cardiac tissues. Studies on heart regeneration in zebrafish and neonatal mice have shown that cardiomyocyte proliferation is essential for replenishing myocardium. We will review recent advancements that have demonstrated the importance of Neuregulin 1/ErbB2 and innervation in regulating cardiomyocyte proliferation using both adult zebrafish and neonatal mouse heart regeneration models. Emerging findings suggest that different populations of macrophages and inflammation might contribute to regenerative versus fibrotic responses. Finally, we will discuss variation in the severity of the cardiac injury and size of the wound, which may explain the range of outcomes observed in different injury models. PMID:27132022

A landscape of circular RNA expression in the human heart.

PubMed

Tan, Wilson L W; Lim, Benson T S; Anene-Nzelu, Chukwuemeka G O; Ackers-Johnson, Matthew; Dashi, Albert; See, Kelvin; Tiang, Zenia; Lee, Dominic Paul; Chua, Wee Woon; Luu, Tuan D A; Li, Peter Y Q; Richards, Arthur Mark; Foo, Roger S Y

2017-03-01

Circular RNA (circRNA) is a newly validated class of single-stranded RNA, ubiquitously expressed in mammalian tissues and possessing key functions including acting as microRNA sponges and as transcriptional regulators by binding to RNA-binding proteins. While independent studies confirm the expression of circRNA in various tissue types, genome-wide circRNA expression in the heart has yet to be described in detail. We performed deep RNA-sequencing on ribosomal-depleted RNA isolated from 12 human hearts, 25 mouse hearts and across a 28-day differentiation time-course of human embryonic stem cell-derived cardiomyocytes. Using purpose-designed bioinformatics tools, we uncovered a total of 15 318 and 3017 cardiac circRNA within human and mouse, respectively. Their abundance generally correlates with the abundance of their cognate linear RNA, but selected circRNAs exist at disproportionately higher abundance. Top highly expressed circRNA corresponded to key cardiac genes including Titin (TTN), RYR2, and DMD. The most abundant cardiac-expressed circRNA is a cytoplasmic localized single-exon circSLC8A1-1. The longest human transcript TTN alone generates up to 415 different exonic circRNA isoforms, the majority (83%) of which originates from the I-band domain. Finally, we confirmed the expression of selected cardiac circRNA by RT-PCR, Sanger sequencing and single molecule RNA-fluorescence in situ hybridization. Our data provide a detailed circRNA expression landscape in hearts. There is a high-abundance of specific cardiac-expressed circRNA. These findings open up a new avenue for future investigation into this emerging class of RNA. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Home blood pressure monitoring among adults-American Heart Association Cardiovascular Health Consumer Survey, 2012.

PubMed

Ayala, Carma; Tong, Xin; Neeley, Eunice; Lane, Rashon; Robb, Karen; Loustalot, Fleetwood

2017-06-01

Home blood pressure monitoring (HBPM) among hypertensive adults was assessed using the 2012 American Heart Association Cardiovascular Health Consumer Survey. The prevalence of hypertension was 25.5% and 53.8% of those reported HBPM. Approximately 63% of hypertensive adults 65 years and older reported HBPM followed by 51% and 34.6% (35-64 and 18-34 years, respectively; P=.001). Those who had seen a healthcare professional within a year reported HBPM compared with those who had not (54.8% vs 32.8%, P=.047). Those who believed that lowering blood pressure can reduce risk of heart attack and stroke had a higher percentage of HBPM compared with those who did not (55.5% vs 33.1%, P=.01). Age and the belief that lowering blood pressure could reduce cardiovascular disease risk were significant factors associated with HBPM. Half of the adult hypertensive patients reported HBPM and its use was greater among those who reported a positive attitude toward lowering blood pressure to reduce cardiovascular disease risk. ©Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

National prevalence of coronary heart disease and its relationship with human development index: A systematic review.

PubMed

Zhu, Ke-Fu; Wang, Yu-Ming; Zhu, Jin-Zhou; Zhou, Qin-Yi; Wang, Ning-Fu

2016-03-01

Coronary heart disease has become a major health concern over the past several decades. Several reviews have assessed the effects of socioeconomic status on the coronary heart disease epidemic in communities and countries, but only a few reviews have been performed at a global level. This study was to explore the relationship between the prevalence of coronary heart disease and socioeconomic development worldwide using the Human Development Index. Systematic review. The data in this study were collected from the MEDLINE database. Cross-sectional studies reporting the prevalence of coronary heart disease until November 2014 were collected. The Human Development Index was sourced from the United Nations Development Programme Database and was used to measure the socioeconomic achievements of countries. Each country was classified as a developing or developed country based on its level of development according to the Human Development Index value. Based on the data analysis on the global level, coronary heart disease prevalence had no association with the national Human Development Index (rho = 0.07). However, there was a positive association between coronary heart disease prevalence and the national Human Development Index in developing countries, although a negative association existed in developed countries (rho = 0.47 and -0.34, respectively). In addition, the past decades have witnessed a growing coronary heart disease epidemic in developing countries, with reverse trends observed in developed countries (P = 0.021 and 0.002, respectively). With the development of socioeconomic status, as measured by the Human Development Index, the prevalence of coronary heart disease is growing in developing countries, while declining in developed countries. Future research needs to pay more attention to the reasonable allocation of medical resources and control of coronary heart disease risk factors. © The European Society of Cardiology 2015.

Left Atrial Appendages from Adult Hearts Contain a Reservoir of Diverse Cardiac Progenitor Cells

PubMed Central

Platt, Yardanna; Helman, Yaron; Feinberg, Yael; Lotan, Chaim; Beeri, Ronen

2013-01-01

Aims There is strong evidence supporting the claim that endogenous cardiac progenitor cells (CPCs) are key players in cardiac regeneration, but the anatomic source and phenotype of the master cardiac progenitors remains uncertain. Our aim was to investigate the different cardiac stem cell populations in the left atrial appendage (LAA) and their fates. Methods and Results We investigated the CPC content and profile of adult murine LAAs using immunohistochemistry and flow cytometry. We demonstrate that the LAA contains a large number of CPCs relative to other areas of the heart, representing over 20% of the total cell number. We grew two distinct CPC populations from the LAA by varying the degree of proteolysis. These differed by their histological location, surface marker profiles and growth dynamics. Specifically, CD45pos cells grew with milder proteolysis, while CD45neg cells grew mainly with more intense proteolysis. Both cell types could be induced to differentiate into cells with cardiomyocyte markers and organelles, albeit by different protocols. Many CD45pos cells expressed CD45 initially and rapidly lost its expression while differentiating. Conclusions Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts. Two different types of CPCs were isolated, differing in their epicardial-myocardial localization. Considering studies demonstrating layer-specific origins of different cardiac progenitor cells, our findings may shed light on possible pathways to study and utilize the diversity of endogenous progenitor cells in the adult heart. PMID:23555001

Guidelines and protocols for cardiovascular magnetic resonance in children and adults with congenital heart disease: SCMR expert consensus group on congenital heart disease

PubMed Central

2013-01-01

Cardiovascular magnetic resonance (CMR) has taken on an increasingly important role in the diagnostic evaluation and pre-procedural planning for patients with congenital heart disease. This article provides guidelines for the performance of CMR in children and adults with congenital heart disease. The first portion addresses preparation for the examination and safety issues, the second describes the primary techniques used in an examination, and the third provides disease-specific protocols. Variations in practice are highlighted and expert consensus recommendations are provided. Indications and appropriate use criteria for CMR examination are not specifically addressed. PMID:23763839

Angiotensin II induces tumor necrosis factor biosynthesis in the adult mammalian heart through a protein kinase C-dependent pathway.

PubMed

Kalra, Dinesh; Sivasubramanian, Natarajan; Mann, Douglas L

2002-05-07

Previous studies suggest that angiotensin II (Ang II) upregulates the expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the effect of Ang II on TNF expression in the adult mammalian heart is not known. To determine whether Ang II was sufficient to provoke TNF biosynthesis in the adult heart, we examined the effects of Ang II in isolated buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF mRNA and protein biosynthesis in the heart as well as in cultured adult cardiac myocytes. The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the activation of nuclear factor-kappaB and activator protein-1 (AP-1), two transcription factors that are important for TNF gene expression. Nuclear factor-kappaB activation was accompanied by phosphorylation of IkappaBalpha on serine 32 as well as degradation of IkappaBalpha, suggesting that the effects of Ang II were mediated through an IkappaBalpha-dependent pathway. The important role of protein kinase C (PKC) was suggested by studies in which a phorbol ester triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF biosynthesis. These studies suggest that Ang II provokes TNF biosynthesis in the adult mammalian heart through a PKC-dependent pathway.

Linking the Heart and the Head: Humanism and Professionalism in Medical Education and Practice.

PubMed

Montgomery, Lynda; Loue, Sana; Stange, Kurt C

2017-05-01

This paper articulates a practical interpretive framework for understanding humanism in medicine through the lens of how it is taught and learned. Beginning with a search for key tensions and relevant insights in the literature on humanism in health professions education, we synthesized a conceptual model designed to foster reflection and action to realize humanistic principles in medical education and practice. The resulting model centers on the interaction between the heart and the head. The heart represents the emotive domains of empathy, compassion, and connectedness. The head represents the cognitive domains of knowledge, attitudes, and beliefs. The cognitive domains often are associated with professionalism, and the emotive domains with humanism, but it is the connection between the two that is vital to humanistic education and practice. The connection between the heart and the head is nurtured by critical reflection and conscious awareness. Four provinces of experience nurture humanism: (1) personal reflection, (2) action, (3) system support, and (4) collective reflection. These domains represent potential levers for developing humanism. Critical reflection and conscious awareness between the heart and head through personal reflection, individual and collective behavior, and supportive systems has potential to foster humanistic development toward healing and health.

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

December 2014 HeartWeek issue of cardiology in the young: highlights of HeartWeek 2014: diseases of the cardiac valves from the foetus to the adult.

PubMed

Jacobs, Jeffrey P

2014-12-01

This December Issue of Cardiology in the Young represents the 12th annual publication generated from the two meetings that compose "HeartWeek in Florida". "HeartWeek in Florida", the joint collaborative project sponsored by the Cardiac Center at the Children's Hospital of Philadelphia, Pennsylvania, together with Johns Hopkins All Children's Heart Institute of Saint Petersburg, Florida, averages over 1000 attendees every year and is now recognised as one of the major planks of continuing medical and nursing education for those working in the fields of diagnosis and treatment of cardiac disease in the foetus, neonate, infant, child, and adult. "HeartWeek in Florida" combines the International Symposium on Congenital Heart Disease, organised by All Children's Hospital and Johns Hopkins Medicine and entering its 15th year, with the Annual Postgraduate Course in Pediatric Cardiovascular Disease, organised by The Children's Hospital of Philadelphia and entering its 18th year. This December, 2014 Issue of Cardiology in the Young features highlights of Johns Hopkins All Children's Heart Institute's 14th Annual International Symposium on Congenital Heart Disease, which was held at the Renaissance Vinoy Resort & Golf Club, Saint Petersburg, Florida, from 15-18 February, 2014. This Symposium was co-sponsored by The American Association for Thoracic Surgery (AATS) and had as its special focus " Diseases of the Cardiac Valves from the Fetus to the Adult ". We acknowledge the tremendous contributions made to paediatric and congenital cardiac care by Duke Cameron and Joel Brenner, and therefore we dedicate this December, 2014 HeartWeek Issue of Cardiology in the Young to them. Duke Cameron is Professor of Surgery at Johns Hopkins University and Cardiac Surgeon-in-Charge at The Johns Hopkins Hospital. Joel Brenner is Professor of Pediatrics at Johns Hopkins University and Director of the Taussig Heart Center at Bloomberg Children's Center, The Johns Hopkins Hospital. Together

Home Health Care With Telemonitoring Improves Health Status for Older Adults with Heart Failure

PubMed Central

Madigan, Elizabeth; Schmotzer, Brian J.; Struk, Cynthia J.; DiCarlo, Christina M.; Kikano, George; Piña, Ileana L.; Boxer, Rebecca S.

2014-01-01

Home telemonitoring can augment home health care services during a patient's transition from hospital to home. Home health care agencies commonly use telemonitors for patients with heart failure although studies have shown mixed results in the use of telemonitors to reduce rehospitalizations. This randomized trial investigated if older patients with heart failure admitted to home health care following a hospitalization would have a reduction in rehospitalizations and improved health status if they received telemonitoring. Patients were followed up to 180 days post-discharge from home health care services. Results showed no difference in the time to rehospitalizations or emergency visits between those who received a telemonitoring vs. usual care. Older heart failure patients who received telemonitoring had better health status by home health care discharge than those who received usual care. Therefore for older adults with heart failure telemonitoring may be important adjunct to home health care services to improve health status. PMID:23438509

Myocardial Infarction in Adults With Congenital Heart Disease.

PubMed

Olsen, Morten; Marino, Bradley; Kaltman, Jonathan; Laursen, Henning; Jakobsen, Lars; Mahle, William; Pearson, Gail; Madsen, Nicolas

2017-12-15

We compared the incidence and 30-day mortality of myocardial infarction (MI) in adults with congenital heart disease (CHD) relative to the general population. This cohort study used nationwide population-based medical databases to identify individuals born before 1982 and diagnosed with CHD in Denmark between 1963 and 2012. Patients were followed for first-time MI using data from the Danish National Registry of Patients. For each subject with CHD, we identified 10 controls from the general population, matched by sex and birth year. A unique personal identifier enabled follow-up for migration, death, or MI. We computed cumulative incidences and hazard ratios (HR) adjusted for birth year and sex for MI and 30-day mortality after MI. We identified 10,501 CHD adults alive at 30 years. By 70 years of age, the cumulative incidence of MI was 10% versus 6.5% for controls. The overall HR of MI in subjects with CHD compared with controls was 2.0 (95% CI 1.7 to 2.3). The 30-day mortality was 18% for the 296 subjects with CHD experiencing an MI during follow-up. The overall HR comparing 30-day mortality after MI between subjects with CHD and controls was 1.4 (95% CI 1.0 to 1.8). The greatest mortality was observed in adults with severe CHD (HR 2.7 [95% CI 1.5 to 5.0]). In conclusion, the incidence of MI and the 30-day mortality after MI for severe CHD were increased in adults with CHD compared with the general population. Underlying mechanisms need to be clarified. Copyright © 2017 Elsevier Inc. All rights reserved.

Awareness of heart attack and stroke symptoms among Hispanic male adults living in the United States.

PubMed

Lutfiyya, May Nawal; Bardales, Ricardo; Bales, Robert; Aguero, Carlos; Brady, Shelly; Tobar, Adriana; McGrath, Cynthia; Zaiser, Julia; Lipsky, Martin S

2010-10-01

There is evidence that Hispanic men are a high risk group for treatment delay for both heart attack and stroke. More targeted research is needed to elucidate this specific population's knowledge of warning signs for these acute events. This study sought to describe within-group disparities in Hispanic men's knowledge of heart attack and stroke symptomology. Multivariate techniques were used to analyze a multi-year Behavioral Risk Factor Surveillance Heart and Stroke module database. The data were cross-sectional and focused on health risk factors and behaviors. The research participants were U.S. male Hispanic adults aged 18-99. The main outcome measure for the study was heart attack and stroke symptom knowledge score. Multivariate logistic regression analysis yielded that Hispanic men aged >or=18 years who earned low scores on the composite heart attack and stroke knowledge questions (range 0-8 points) were more likely to: have less than a high school education, have deferred medical care because of cost, not have an identified health care provider, and be uninsured. There were significant within-group differences. Targeting educational efforts toward older (>or=55 years) Hispanic men with less than high school education, those who do not have an identified health care provider or health insurance, and who defer health care because of cost could be ways to improve the outcome of acute vascular events among the U.S. Hispanic adult male population.

Prevalence of Cancer in Adults With Congenital Heart Disease Compared With the General Population.

PubMed

Gurvitz, Michelle; Ionescu-Ittu, Raluca; Guo, Liming; Eisenberg, Mark J; Abrahamowicz, Michal; Pilote, Louise; Marelli, Ariane J

2016-12-01

The prevalence rate of cancer among adult patients with congenital heart disease (CHD) in North America has not been previously described. The Quebec adult CHD database was used to determine the prevalence rate of cancer among adult patients with CHD measured as the number of adults with CHD and cancer alive in 2005 per 1,000 adults with CHD. This prevalence rate was compared with the prevalence rate of cancer in the general population of adults in Canada. Types of cancer among the CHD group were described by gender and age. Adult patients with CHD had a 1.6 to 2 times higher prevalence of cancer at 2, 5, and 10 years for both men and women. Overall, men had a greater prevalence of total cancers in all-time durations than did women. Breast, colon, and prostate cancer were the most common cancers reported in adults with CHD. In conclusion, we observed an increased prevalence of cancer among the adult CHD population of Quebec compared with the general Canadian population. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinicians' perspectives on patient satisfaction in adult congenital heart disease clinics--a dimension of health care quality whose time has come.

PubMed

Rozenblum, Ronen; Gianola, Ann; Ionescu-Ittu, Raluca; Verstappen, Amy; Landzberg, Michael; Gurvitz, Michelle; Jenkins, Kathy; Bates, David W; Marelli, Ariane J

2015-01-01

Patient-centered care and patient satisfaction represent key dimensions of health care quality. This is relevant for the growing number of patients with life-long conditions. In the present study, our goal was to examine clinicians' attitudes and behavior with respect to patient satisfaction in adult congenital heart disease outpatient clinics. A 34-question survey was developed to assess adult congenital heart disease clinicians' awareness, attitudes, and behavior relative to patient satisfaction and administered in-person or online to clinicians from the largely U.S.-based Adult Congenital Heart Association's database of adult congenital heart disease health care providers. Overall, 267 questionnaires were filled out: 108 were collected in person (79% response rate) and 159 online (17.5% response rate). Responses were received from physicians (161); nurses (73); physician assistants (20); and others (13). Although 85% of clinicians believed it was important to inquire about patient satisfaction, only 28% reported routinely inquiring about this dimension of care. Only 34% claimed they had adequate training to cope with varying levels of patient satisfaction, 44% stated that their department utilized patient satisfaction surveys, and 37% received feedback from the hospital management in the preceding 12 months. In multivariate analyses, clinicians that received feedback from the hospital management and had adequate training were more likely to inquire about patient satisfaction. Although patient satisfaction is perceived as an important dimension of quality care by adult congenital heart disease clinicians, most of them reported insufficient institutional support to achieve this. Our findings suggest that clinicians would benefit from health care organizations engaging them in the delivery of this dimension of health care quality. © 2014 Wiley Periodicals, Inc.

Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart

PubMed Central

Malliaras, Konstantinos; Zhang, Yiqiang; Seinfeld, Jeffrey; Galang, Giselle; Tseliou, Eleni; Cheng, Ke; Sun, Baiming; Aminzadeh, Mohammad; Marbán, Eduardo

2013-01-01

Cardiosphere-derived cells (CDCs) have been shown to regenerate infarcted myocardium in patients after myocardial infarction (MI). However, whether the cells of the newly formed myocardium originate from the proliferation of adult cardiomyocytes or from the differentiation of endogenous stem cells remains unknown. Using genetic fate mapping to mark resident myocytes in combination with long-term BrdU pulsing, we investigated the origins of postnatal cardiomyogenesis in the normal, infarcted and cell-treated adult mammalian heart. In the normal mouse heart, cardiomyocyte turnover occurs predominantly through proliferation of resident cardiomyocytes at a rate of ∼1.3–4%/year. After MI, new cardiomyocytes arise from both progenitors as well as pre-existing cardiomyocytes. Transplantation of CDCs upregulates host cardiomyocyte cycling and recruitment of endogenous progenitors, while boosting heart function and increasing viable myocardium. The observed phenomena cannot be explained by cardiomyocyte polyploidization, bi/multinucleation, cell fusion or DNA repair. Thus, CDCs induce myocardial regeneration by differentially upregulating two mechanisms of endogenous cell proliferation. PMID:23255322

Adult congenital heart disease imaging with second-generation dual-source computed tomography: initial experiences and findings.

PubMed

Ghoshhajra, Brian B; Sidhu, Manavjot S; El-Sherief, Ahmed; Rojas, Carlos; Yeh, Doreen Defaria; Engel, Leif-Christopher; Liberthson, Richard; Abbara, Suhny; Bhatt, Ami

2012-01-01

Adult congenital heart disease patients present a unique challenge to the cardiac imager. Patients may present with both acute and chronic manifestations of their complex congenital heart disease and also require surveillance for sequelae of their medical and surgical interventions. Multimodality imaging is often required to clarify their anatomy and physiology. Radiation dose is of particular concern in these patients with lifelong imaging needs for their chronic disease. The second-generation dual-source scanner is a recently available advanced clinical cardiac computed tomography (CT) scanner. It offers a combination of the high-spatial resolution of modern CT, the high-temporal resolution of dual-source technology, and the wide z-axis coverage of modern cone-beam geometry CT scanners. These advances in technology allow novel protocols that markedly reduce scan time, significantly reduce radiation exposure, and expand the physiologic imaging capabilities of cardiac CT. We present a case series of complicated adult congenital heart disease patients imaged by the second-generation dual-source CT scanner with extremely low-radiation doses and excellent image quality. © 2012 Wiley Periodicals, Inc.

Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

PubMed

Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

2015-06-01

Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i

The human heart: application of the golden ratio and angle.

PubMed

Henein, Michael Y; Zhao, Ying; Nicoll, Rachel; Sun, Lin; Khir, Ashraf W; Franklin, Karl; Lindqvist, Per

2011-08-04

The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Altered myocardial force generation in end-stage human heart failure.

PubMed

Papp, Zoltán; van der Velden, Jolanda; Borbély, Attila; Édes, István; Stienen, Ger J M

2014-12-01

This study aimed to elucidate the molecular background of increased Ca 2+ sensitivity of force production in cardiomyocytes of end-stage human heart failure. Ca 2+ -activated isometric force and the cross-bridge specific rate of force redevelopment (k tr ) were determined in Triton-skinned myocytes from end-stage failing and non-failing donor hearts. Measurements (control: pH 7.2, 0 mM inorganic phosphate (P i )) were performed under test conditions that probed either the Ca 2+ -regulatory function of the thin filaments (pH 6.5), the kinetics of the actin-myosin cross-bridge cycle (10 mM P i ), or both (pH 6.5, 10 mM P i ). The control maximal Ca 2+ -activated force (F o ) and k trmax did not differ between failing and non-failing myocytes. At submaximal [Ca 2+ ], however, both force and k tr were higher in failing than in donor myocytes. The difference in the Ca 2+ sensitivities of force production was preserved when the thin filament regulatory function was perturbed by acidosis (pH 6.5) but was abolished by cross-bridge modulation (i.e. by P i ) both at pH 7.2 and at pH 6.5. P i induced a larger reduction in force but a smaller increase in k tr in the failing myocytes than in the non-failing myocytes at submaximal [Ca 2+ ]. The enhanced P i sensitivity of the actin-myosin interaction suggests that the P i release step of the actin-myosin cross-bridge cycle is modified during end-stage human heart failure. This might be of functional importance when P i accumulates (e.g. during cardiac ischaemia). Moreover, this alteration can influence cardiac energetics and the clinical efficacy of sarcomere targeted agents in human heart failure. © 2015 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Free fatty acid metabolism of the human heart at rest

PubMed Central

Most, Albert S.; Brachfeld, Norman; Gorlin, Richard; Wahren, John

1969-01-01

Myocardial substrate metabolism was studied in 13 subjects at the time of diagnostic cardiac catheterization by means of palmitic acid-14C infusion with arterial and coronary sinus sampling. Two subjects were considered free of cardiac pathology and all, with one exception, demonstrated lactate extraction across the portion of heart under study. Data for this single lactate-producing subject were treated separately. The fractional extraction of 14C-labeled free fatty acids (FFA) (44.4±9.5%) was nearly twice that of unlabeled FFA (23.2±7.8%) and raised the possibility of release of FFA into the coronary sinus. FFA uptake, based on either the arterial minus coronary sinus concentration difference or the FFA-14C fractional extraction, was directly proportional to the arterial FFA concentration. Gas-liquid chromatography failed to demonstrate selective handling of any individual FFA by the heart. Fractional oxidation of FFA was 53.5±12.7%, accounting for 53.2±14.4% of the heart's oxygen consumption while nonlipid substrates accounted for an additional 30.0±17.3%. Determinations of both labeled and unlabeled triglycerides suggested utilization of this substrate by the fasting human heart. Direct measurement of FFA fractional oxidation as well as FFA uptake, exclusive of possible simultaneous FFA release, would appear necessary in studies concerned with human myocardial FFA metabolism. PMID:5794244

Engineering human ventricular heart muscles based on a highly efficient system for purification of human pluripotent stem cell-derived ventricular cardiomyocytes.

PubMed

Li, Bin; Yang, Hui; Wang, Xiaochen; Zhan, Yongkun; Sheng, Wei; Cai, Huanhuan; Xin, Haoyang; Liang, Qianqian; Zhou, Ping; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yang, Pengyuan; Zhang, Jianyi; Shou, Weinian; Huang, Guoying; Liang, Ping; Sun, Ning

2017-09-29

Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish. The purification system used TALEN-mediated genomic editing techniques to insert the neomycin or EGFP selection marker directly after the myosin light chain 2 (MYL2) locus in human pluripotent stem cells. Purified early ventricular cardiomyocytes were estimated by immunofluorescence, fluorescence-activated cell sorting, quantitative PCR, microelectrode array, and patch clamp. In subsequent experiments, the mixture of mature MYL2-positive ventricular cardiomyocytes and mesenchymal cells were cocultured with decellularized natural heart matrix. Histological and electrophysiology analyses of the formed tissues were performed 2 weeks later. Human ventricular cardiomyocytes were efficiently isolated based on the purification system using G418 or flow cytometry selection. When combined with the decellularized natural heart matrix as the scaffold, functional human ventricular heart muscles were prepared in a dish. These engineered human ventricular muscles can be great tools for regenerative therapy of human ventricular damage as well as drug screening and ventricular-specific disease modeling in the future.

Left Recumbent Position Decreases Heart Rate without Alterations in Cardiac Autonomic Nervous System Activity in Healthy Young Adults.

PubMed

Sasaki, Konosuke; Haga, Mayu; Endo, Yoichi; Fujiwara, Junko; Maruyama, Ryoko

2017-04-01

Some studies have reported that recumbent position may have advantages in patients with heart disease and in pregnancy. However, it remains controversial whether recumbent position affects autonomic nervous system activity and hemodynamics in healthy adults. The aim of this study was to evaluate alterations in heart rate variability (HRV) and hemodynamics in the supine, left recumbent and right recumbent positions in healthy young adults. A total of 80 participants aged 22.8 ± 3.1 years were enrolled in this observational study. Fifty-eight volunteers (29 men and 29 women) maintained the supine position followed by the left and right recumbent positions, while electrocardiographic data were recorded for spectral analysis of HRV to assess cardiac vagal nerve and sympathetic nerve activities. The heart rate (HR) was significantly lower in the left recumbent position than in the other positions. There were no statistically significant differences in HRV among the three positions. Considering the possibility that the echographic procedure affects autonomic nervous system (ANS) activity, the other 22 participants (11 men and 11 women) underwent an echographic evaluation of hemodynamics in the heart and inferior vena cava (IVC) across the three positions. Although a low HR was also observed, there were no statistically significant differences in the IVC or the heart blood volume between the supine and the left recumbent positions. A postural change to the left recumbent position does not affect the cardiac blood circulation or ANS activity, though it does decrease HR in healthy young adults. This finding indicates that the lower HR in the left recumbent position is not attributable to the ANS activity.

Oracle, a novel PDZ-LIM domain protein expressed in heart and skeletal muscle.

PubMed

Passier, R; Richardson, J A; Olson, E N

2000-04-01

In order to identify novel genes enriched in adult heart, we performed a subtractive hybridization for genes expressed in mouse heart but not in skeletal muscle. We identified two alternative splicing variants of a novel PDZ-LIM domain protein, which we named Oracle. Both variants contain a PDZ domain at the amino-terminus and three LIM domains at the carboxy-terminus. Highest homology of Oracle was found with the human and rat enigma proteins in the PDZ domain (62 and 61%, respectively) and in the LIM domains (60 and 69%, respectively). By Northern hybridization analysis, we showed that expression is highest in adult mouse heart, low in skeletal muscle and undetectable in other adult mouse tissues. In situ hybridization in mouse embryos confirmed and extended these data by showing high expression of Oracle mRNA in atrial and ventricular myocardial cells from E8.5. From E9.5 low expression of Oracle mRNA was detectable in myotomes. These data suggest a role for Oracle in the early development and function of heart and skeletal muscle.

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

Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

PubMed

Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

2017-10-01

Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Contemporary cardiac surgery for adults with congenital heart disease.

PubMed

Beurtheret, Sylvain; Tutarel, Oktay; Diller, Gerhard Paul; West, Cathy; Ntalarizou, Evangelia; Resseguier, Noémie; Papaioannou, Vasileios; Jabbour, Richard; Simpkin, Victoria; Bastin, Anthony J; Babu-Narayan, Sonya V; Bonello, Beatrice; Li, Wei; Sethia, Babulal; Uemura, Hideki; Gatzoulis, Michael A; Shore, Darryl

2017-08-01

Advances in early management of congenital heart disease (CHD) have led to an exponential growth in adults with CHD (ACHD). Many of these patients require cardiac surgery. This study sought to examine outcome and its predictors for ACHD cardiac surgery. This is an observational cohort study of prospectively collected data on 1090 consecutive adult patients with CHD, undergoing 1130 cardiac operations for CHD at the Royal Brompton Hospital between 2002 and 2011. Early mortality was the primary outcome measure. Midterm to longer-term survival, cumulative incidence of reoperation, other interventions and/or new-onset arrhythmia were secondary outcome measures. Predictors of early/total mortality were identified. Age at surgery was 35±15 years, 53% male, 52.3% were in New York Heart Association (NYHA) class I, 37.2% in class II and 10.4% in class III/IV. Early mortality was 1.77% with independent predictors NYHA class ≥ III, tricuspid annular plane systolic excursion (TAPSE) <15 mm and female gender. Over a mean follow-up of 2.8±2.6 years, 46 patients died. Baseline predictors of total mortality were NYHA class ≥ III, TAPSE <15 mm and non-elective surgery. The number of sternotomies was not independently associated with neither early nor total mortality. At 10 years, probability of survival was 94%. NYHA class among survivors was significantly improved, compared with baseline. Contemporary cardiac surgery for ACHD performed at a single, tertiary reference centre with a multidisciplinary approach is associated with low mortality and improved functional status. Also, our findings emphasise the point that surgery should not be delayed because of reluctance to reoperate only. © 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.

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

PubMed

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

2014-01-01

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

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males.

PubMed

Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

2016-11-29

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, 'stoned', 'want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

PubMed Central

Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

2016-01-01

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

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.

Choice and competition between adult congenital heart disease centers: evidence of considerable geographical disparities and association with clinical or academic results.

PubMed

Diller, Gerhard-Paul; Kempny, Aleksander; Piorkowski, Adam; Grübler, Martin; Swan, Lorna; Baumgartner, Helmut; Dimopoulos, Konstantinos; Gatzoulis, Michael A

2014-03-01

Although concentrating adult congenital heart disease services at high-volume centers has been widely advocated, the potential beneficial effects of competition and patient choice have received relatively little attention. We aimed to assess the degree of patient choice and competition between adult congenital heart disease units and to investigate whether competition indices correlate with clinical quality or research output. Competition between the 10 major adult congenital heart disease units in England was evaluated based on the Herfindahl-Hirschman Index, representing the sum of squared market shares of individual units. In addition, to account for geography and feasible access, we calculated spatial indices of competition based on travel time by road. These indices were correlated with 30-day mortality postpulmonary valve replacement in adult patients (as obtained from the National Central Cardiac Audit Database) and the aggregate research impact factors of individual centers. On a national level, a high level of competition without obvious dominant players was found (Herfindahl-Hirschman Index between 0.107 and 0.013). When accounting for geography, however, important disparities in patient choice and competition faced by individual centers emerged. The degree of local competition was correlated significantly with clinical outcomes and research output. In contrast, no association between center volume and outcome could be established. Beyond the usual focus on concentrating services at high-volume centers, the potentially beneficial effects of competition should not be ignored. Therefore, policymakers should consider fostering a competitive environment for adult congenital heart disease centers or at least avoiding creating government-granted monopolies in the field.

ILK Induces Cardiomyogenesis in the Human Heart

PubMed Central

Traister, Alexandra; Aafaqi, Shabana; Masse, Stephane; Dai, Xiaojing; Li, Mark; Hinek, Aleksander; Nanthakumar, Kumaraswamy; Hannigan, Gregory; Coles, John G.

2012-01-01

Background Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart. Methodology/Principal Findings Primary cultures of human fetal myocardial cells (19–22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk×2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C×43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILKR211A) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILKWT). The cardiomyogenic effects of ILKR211A and ILKWT were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILKR211A and ILKWT. Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs). Conclusions/Significance In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the

Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish.

PubMed

González-Rosa, Juan Manuel; Sharpe, Michka; Field, Dorothy; Soonpaa, Mark H; Field, Loren J; Burns, Caroline E; Burns, C Geoffrey

2018-02-26

Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant-negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

The Impact of Obesity on Postoperative Outcomes in Adults with Congenital Heart Disease Undergoing Pulmonary Valve Replacement.

PubMed

Buelow, Matthew W; Earing, Michael G; Hill, Garick D; Cohen, Scott B; Bartz, Peter J; Tweddell, James S; Ginde, Salil

2015-01-01

The impact of obesity on surgical morbidity in adults with congenital heart disease is currently unknown. The aim of our study was to investigate the impact of obesity on postoperative outcomes in adults with congenital heart disease undergoing reoperation for pulmonary valve replacement. A retrospective analysis was performed assessing the influence of obesity on surgical outcomes. Obesity was defined as a body mass index ≥30 kg/m2. The mean body mass index of the cohort was 25.9 ± 6.9 kg/m2 . The cohort included 71 patients with 17 patients (24%) being obese. There was no postoperative mortality. Obese patients had a longer hospital length of stay (6.6 vs. 4.7 days; P < .001) and increased incidence of postoperative arrhythmias (29% vs. 5.6%; P = .003) compared with nonobese patients. Multivariable analysis performed using logistic regression with backwards elimination demonstrated obesity was independently associated with hospital length of stay >5 days (odds ratio [OR] = 5.2; 95% confidence interval [CI]: 1.5-18.2, P = .01) and with increased postoperative arrhythmias (OR = 4.2; 95% CI: 1.7-40, P < .01). Obesity is associated with increased morbidity in adults with congenital heart disease undergoing pulmonary valve replacement, including longer hospitalization and higher risk for postoperative arrhythmias. © 2015 Wiley Periodicals, Inc.

Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

PubMed

Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

2013-01-01

Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

Utility of 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines in HIV-Infected Adults With Carotid Atherosclerosis.

PubMed

Phan, Binh An P; Weigel, Bernard; Ma, Yifei; Scherzer, Rebecca; Li, Danny; Hur, Sophia; Kalapus, S C; Deeks, Steven; Hsue, Priscilla

2017-07-01

Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque. Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39-49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%; P <0.001), in those with plaque (32% versus 17%; P =0.0002), and in those without plaque (16% versus 7%; P =0.025). In multivariable analysis, older age, higher low-density lipoprotein cholesterol, pack per year of smoking, and history of opportunistic infection were associated with baseline plaque. Baseline IMT (hazard ratio, 1.18 per 10% increment; 95% confidence interval, 1.05-1.33; P =0.005) and plaque (hazard ratio, 2.06; 95% confidence interval, 1.02-4.08; P =0.037) were each associated with all-cause mortality, independent of traditional CVD risk factors. Although the American College of Cardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection

Disparities in adult awareness of heart attack warning signs and symptoms--14 states, 2005.

PubMed

2008-02-22

In 2005, approximately 920,000 persons in the United States had a myocardial infarction (i.e., heart attack); in 2004, approximately 157,000 heart attacks were fatal. One study indicated that approximately half of cardiac deaths occur within 1 hour of symptom onset, before patients reach a hospital. Timely access to emergency cardiac care, receipt of advanced treatment, and potential for surviving a heart attack all depend on 1) early recognition of warning signs and symptoms of a heart attack by persons who are having a heart attack and bystanders and 2) immediately calling 9-1-1. Healthy People 2010 includes an objective to increase from 46% to 50% the proportion of adults aged > or =20 years who are aware of the early warning signs and symptoms of a heart attack and the importance of accessing rapid emergency care by calling 9-1-1 (objective 12-2). To update estimates of public awareness of heart attack warning signs and symptoms and knowledge of the importance of calling 9-1-1, CDC analyzed 2005 Behavioral Risk Factor Surveillance System (BRFSS) data from the 14 states that included questions on signs and symptoms of a heart attack. This report describes the results of that analysis, which indicated that although the awareness of certain individual warning signs was as high as 93% (i.e., for shortness of breath), awareness of all five warning signs was 31%, underscoring the need for public health measures to increase public awareness of heart attack warning signs and symptoms. In addition, disparities in awareness were observed by race/ethnicity, sex, and level of education, suggesting that new public health measures should target populations with the lowest levels of awareness.

Congenital heart defect causing mutation in Nkx2.5 displays in vivo functional deficit.

PubMed

Zakariyah, Abeer F; Rajgara, Rashida F; Veinot, John P; Skerjanc, Ilona S; Burgon, Patrick G

2017-04-01

The Nkx2.5 gene encodes a transcription factor that plays a critical role in heart development. In humans, heterozygous mutations in NKX2.5 result in congenital heart defects (CHDs). However, the molecular mechanisms by which these mutations cause the disease remain unknown. NKX2.5-R142C is a mutation that was reported to be associated with atrial septal defect (ASD) and atrioventricular (AV) block in 13-patients from one family. The R142C mutation is located within both the DNA-binding domain and the nuclear localization sequence of NKX2.5 protein. The pathogenesis of CHDs in humans with R142C point mutation is not well understood. To examine the functional deficit associated with this mutation in vivo, we generated and characterized a knock-in mouse that harbours the human mutation R142C. Systematic structural and functional examination of the embryonic, newborn, and adult mice revealed that the homozygous embryos Nkx2.5 R141C/R141C are developmentally arrested around E10.5 with delayed heart morphogenesis and downregulation of Nkx2.5 target genes, Anf, Mlc2v, Actc1 and Cx40. Histological examination of Nkx2.5 R141C/+ newborn hearts showed that 36% displayed ASD, with at least 80% 0f adult heterozygotes displaying a septal defect. Moreover, heterozygous Nkx2.5 R141C/+ newborn mice have downregulation of ion channel genes with 11/12 adult mice manifesting a prolonged PR interval that is indicative of 1st degree AV block. Collectively, the present study demonstrates that mice with the R141C point mutation in the Nkx2.5 allele phenocopies humans with the NKX2.5 R142C point mutation. Copyright © 2017 Elsevier Ltd. All rights reserved.

How the expression of green fluorescent protein and human cardiac actin in the heart influences cardiac function and aerobic performance in zebrafish Danio rerio.

PubMed

Avey, S R; Ojehomon, M; Dawson, J F; Gillis, T E

2018-01-01

The present study examined how the expression of enhanced green fluorescent protein (eGFP) and human cardiac actin (ACTC) in zebrafish Danio rerio influences embryonic heart rate (R H ) and the swim performance and metabolic rate of adult fish. Experiments with the adults involved determining the critical swimming speed (U crit , the highest speed sustainable and measure of aerobic capacity) while measuring oxygen consumption. Two different transgenic D. rerio lines were examined: one expressed eGFP in the heart (tg(cmlc:egfp)), while the second expressed ACTC in the heart and eGFP throughout the body (tg(cmlc:actc,ba:egfp)). It was found that R H was significantly lower in the tg(cmlc:actc,ba:egfp) embryos 4 days post-fertilization compared to wild-type (WT) and tg(cmlc:egfp). The swim experiments demonstrated that there was no significant difference in U crit between the transgenic lines and the wild-type fish, but metabolic rate and cost of transport (oxygen used to travel a set distance) was nearly two-fold higher in the tg(cmlc:actc,ba:egfp) fish compared to WT at their respective U crit . These results suggest that the expression of ACTC in the D. rerio heart and the expression of eGFP throughout the animal, alters cardiac function in the embryo and reduces the aerobic efficiency of the animal at high levels of activity. © 2017 The Fisheries Society of the British Isles.

Myocardial Parvovirus B19 Persistence: Lack of Association with Clinicopathologic Phenotype in Adults with Heart Failure

PubMed Central

Stewart, Garrick C.; Lopez-Molina, Javier; Gottumukkala, Raju V.; Rosner, Gregg F.; Anello, Mary S.; Hecht, Jonathan L.; Winters, Gayle L.; Padera, Robert F.; Baughman, Kenneth L.; Lipes, Myra A.

2011-01-01

Background Multiple viruses have been isolated from the heart, but their significance remains controversial. We sought to determine the prevalence of cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult heart failure (HF) patients and to define the clinicopathologic profile of patients exhibiting viral positivity. Methods and Results EMB from 100 patients (median EF 30%, IQR 20–45%) presenting for cardiomyopathy evaluation (median symptom duration 5 months, IQR 1–13 months) were analyzed by polymerase chain reaction for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each isolate was sequenced and viral load was determined. Parvovirus B19 was the only virus detected in EMB samples (12% of subjects). No subject had anti-parvovirus IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The clinical presentation of parvovirus-positive patients was markedly heterogeneous, with both acute and chronic HF, variable ventricular function, and ischemic cardiomyopathy. No subject met Dallas histopathological criteria for active or borderline myocarditis. Two patients with a positive cardiac MRI and presumed “parvomyocarditis” had similar viral loads as autopsy controls without heart disease. The oldest parvovirus-positive subjects were positive for genotype 2, suggesting lifelong persistence in heart tissue. Conclusions Parvovirus B19 was the only virus isolated from EMB samples in this series of adult HF patients from the United States. Positivity was associated with a wide array of clinical presentations and heart failure phenotypes. Our studies do not support a causative role for parvovirus B19 persistence in HF and therefore advocate against the use of antiviral therapy for these patients. PMID:21097605

Arrhythmias in Adults with Congenital Heart Disease: What Are Risk Factors for Specific Arrhythmias?

PubMed

Loomba, Rohit S; Buelow, Matthew W; Aggarwal, Saurabh; Arora, Rohit R; Kovach, Joshua; Ginde, Salil

2017-04-01

An increasing number of patients with congenital heart disease are now surviving into adulthood. This has also led to the emergence of complications from the underlying congenital heart disease, related surgical interventions, and associated combordities. While the prevalence of particular arrhythmias with specific congenital heart disease has been previously described, a detailed analysis of all lesions and a large number of comorbidities has not been previously published. Admissions with congenital heart disease were identified in the National Inpatient Sample. Associated comorbidities were also identified for these patients. Univariate analysis was done to compare those risk factors associated with specific arrhythmias in the setting of congenital heart disease. Next, regression analysis was done to identify what patient characteristics and comorbidities were associated with increased risk of specific arrhythmias. A total of 52,725,227 admissions were included in the analysis. Of these, 109,168 (0.21%) had congenital heart disease. Of those with congenital heart disease, 27,088 (25%) had an arrhythmia at some point. The most common arrhythmia in those with congenital heart disease was atrial fibrillation, which was noted in 86% of those with arrhythmia followed by atrial flutter which was noted in 20% of those with congenital heart disease. The largest burden of arrhythmia was found to be in those with tricuspid atresia with a 51% prevalence of arrhythmia in this group followed by Ebstein anomaly which had an arrhythmia prevalence of 39%. Increasing age, male gender, double outlet right ventricle, atrioventricular septal defect, heart failure, obstructive sleep apnea, transposition of the great arteries, congenitally corrected transposition, and tetralogy of Fallot were frequently noted to be independent risk factors of specific arrhythmias. Approximately, 25% of adult admissions with congenital heart disease are associated with arrhythmia. The burden of

Atrial tachyarrhythmia in adult congenital heart disease

PubMed Central

Karbassi, Arsha; Nair, Krishnakumar; Harris, Louise; Wald, Rachel M; Roche, S Lucy

2017-01-01

The adult congenital heart disease (ACHD) population continues to grow and most cardiologists, emergency room physicians and family doctors will intermittently come into contact with these patients. Oftentimes this may be in the setting of a presentation with atrial tachyarrhythmia; one of the commonest late complications of ACHD and problem with potentially serious implications. Providing appropriate initial care and ongoing management of atrial tachyarrhythmia in ACHD patients requires a degree of specialist knowledge and an awareness of certain key issues. In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the underlying heart defect and often occurs as a result of surgical scar or a consequence of residual hemodynamic or electrical disturbances. Arrhythmias significantly increase mortality and morbidity in ACHD and are the most frequent reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial fibrillation are the most prevalent type of arrhythmia in this patient group. In hemodynamically unstable patients, urgent cardioversion is required. Acute management of the stable patient includes anticoagulation, rate control, and electrical or pharmacological cardioversion. In ACHD, rhythm control is the preferred management strategy and can often be achieved. However, in the long-term, medication side-effects can prove problematic. Electrophysiology studies and catheter ablation are important treatments modalities and in certain cases, surgical or percutaneous treatment of the underlying cardiac defect has a role. ACHD patients, especially those with complex CHD, are at increased risk of thromboembolic events and anticoagulation is usually required. Female ACHD patients of child bearing age may wish to pursue pregnancies. The risk of atrial arrhythmias is increased during pregnancy and management of atrial tachyarrhythmia during pregnancy needs specific consideration. PMID:28706585

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

PubMed

Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

2015-06-27

The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Health care resource utilization in adults with congenital heart disease.

PubMed

Mackie, Andrew S; Pilote, Louise; Ionescu-Ittu, Raluca; Rahme, Elham; Marelli, Ariane J

2007-03-15

The number of adults with congenital heart disease (CHD) is increasing. However, rates of health care resource utilization in this population are unknown. The objectives of this study were to describe the use of general health care resources in adults with CHD and to examine the impact of CHD severity on resource utilization. The study consisted of adults alive in 1996 who had > or = 1 diagnosis of a CHD lesion conforming to the International Classification of Disease, Ninth Revision, in the physician's claims database of the province of Quebec from 1983 to 2000. From 1996 to 2000, rates of health care utilization were measured. The impact of the severity of CHD on the use of health care resources was determined using multivariate models to adjust for age, gender, Charlson co-morbidity score, and duration of follow-up. The study population consisted of 22,096 adults with CHD (42% men). From 1996 to 2000, 87% received outpatient care from specialists, 68% visited emergency rooms, 51% were hospitalized, and 16% were admitted to critical care units. Patients with severe CHD had higher adjusted rates of outpatient cardiologist care (rate ratio [RR] 2.24, 95% confidence interval [CI] 2.06 to 2.45), emergency department utilization (RR 1.09, 95% CI 1.03 to 1.17), hospitalization (RR 1.30, 95% CI 1.19 to 1.43), and days in critical care (RR 2.12, 95% CI 1.80 to 2.50) than patients with other congenital cardiac lesions. Hospitalization rates were higher than in the general Quebec adult population (RR 2.08, 95% CI 2.00 to 2.17). In conclusion, adults with CHD have high rates of health care resource utilization, particularly those with severe lesions. Appropriate resource allocation is required to serve this growing population.

Heart regeneration.

PubMed

Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

2016-07-01

Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2015 Elsevier B.V. All rights reserved.

Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

PubMed

Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

2015-11-01

Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations. Copyright © 2015 Elsevier Inc. All rights reserved.

Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury.

PubMed

Szczepanek, Karol; Allegood, Jeremy; Aluri, Hema; Hu, Ying; Chen, Qun; Lesnefsky, Edward J

2016-04-01

The content and composition of cardiolipin (CL) is critical for preservation of mitochondrial oxidative phosphorylation (OXPHOS) and inner membrane integrity. Tafazzin (Taz) is an enzyme responsible for remodeling of immature CL containing mixed acyl groups into the mature tetralinoleyl form (C18:2)4-CL. We hypothesized that acquired defects in Taz in the mature heart would impact remodeling of CL and augment cardiac injury. The role of acquired Taz deficiency was studied using the inducible Taz knockdown (TazKD) mouse. Taz-specific shRNA is induced by doxycycline (DOX). One day of DOX intake decreased Taz mRNA in the heart to 20% vs. DOX-treated WT. Knockdown was initiated at an adult age and was stable during long term feeding. CL phenotype was assessed by (C18:2)4-CL content and was reduced 40% vs. WT at two months of DOX. TazKD showed increased production of reactive oxygen species and increased susceptibility to permeability transition pore opening at baseline. However, OXPHOS measured using the rate of oxygen consumption was unchanged in the setting of acquired Taz deficiency. Infarct size, measured in isolated buffer-perfused Langendorff hearts following 25min. Stop flow ischemia and 60min. Reperfusion was not altered in TazKD hearts. Thus, impaired Taz-function with onset at adult age does not enhance susceptibility to ischemia-reperfusion injury. Published by Elsevier B.V.

Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

PubMed Central

Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

2011-01-01

Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

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

Associations of Subjective Sleep Quality and Daytime Sleepiness With Cognitive Impairment in Adults and Elders With Heart Failure.

PubMed

Byun, Eeeseung; Kim, Jinyoung; Riegel, Barbara

2017-01-01

This study examined the association of subjective nighttime sleep quality and daytime sleepiness with cognitive impairment in 105 adults (< 60 years old) and 167 elders (≥ 60 years old) with heart failure. Nighttime sleep quality and daytime sleepiness were measured by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Cognitive impairment was assessed using a neuropsychological battery measuring attention, memory, and processing speed. Multivariate logistic regression was used. In adults, daytime sleepiness was associated with cognitive impairment, whereas poor nighttime sleep quality was associated with cognitive impairment in elders. Age may play an important role in how sleep impacts cognition in persons with heart failure. Improving nighttime sleep quality and daytime sleepiness in this population may improve cognition.

2017 American Heart Association Focused Update on Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

PubMed

Kleinman, Monica E; Goldberger, Zachary D; Rea, Thomas; Swor, Robert A; Bobrow, Bentley J; Brennan, Erin E; Terry, Mark; Hemphill, Robin; Gazmuri, Raúl J; Hazinski, Mary Fran; Travers, Andrew H

2018-01-02

Cardiopulmonary resuscitation is a lifesaving technique for victims of sudden cardiac arrest. Despite advances in resuscitation science, basic life support remains a critical factor in determining outcomes. The American Heart Association recommendations for adult basic life support incorporate the most recently published evidence and serve as the basis for education and training for laypeople and healthcare providers who perform cardiopulmonary resuscitation. © 2017 American Heart Association, Inc.

Desensitization strategies in adult heart transplantation-Will persistence pay off?

PubMed

Chih, Sharon; Patel, Jignesh

2016-08-01

Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. 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

Myostatin regulates energy homeostasis in the heart and prevents heart failure.

PubMed

Biesemann, Nadine; Mendler, Luca; Wietelmann, Astrid; Hermann, Sven; Schäfers, Michael; Krüger, Marcus; Boettger, Thomas; Borchardt, Thilo; Braun, Thomas

2014-07-07

Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes, including enhanced insulin sensitivity. However, the function of myostatin in the heart is barely understood, although it is upregulated in the myocardium under several pathological conditions. Here, we aimed to decipher the role of myostatin and myostatin-dependent signaling pathways for cardiac function and cardiac metabolism in adult mice. To avoid potential counterregulatory mechanisms occurring in constitutive and germ-line-based myostatin mutants, we generated a mouse model that allows myostatin inactivation in adult cardiomyocytes. Cardiac MRI revealed that genetic inactivation of myostatin signaling in the adult murine heart caused cardiac hypertrophy and heart failure, partially recapitulating effects of the age-dependent decline of the myostatin paralog growth and differentiation factor 11. We found that myostatin represses AMP-activated kinase activation in the heart via transforming growth factor-β-activated kinase 1, thereby preventing a metabolic switch toward glycolysis and glycogen accumulation. Furthermore, myostatin stimulated expression of regulator of G-protein signaling 2, a GTPase-activating protein that restricts Gaq and Gas signaling and thereby protects against cardiac failure. Inhibition of AMP-activated kinase in vivo rescued cardiac hypertrophy and prevented enhanced glycolytic flow and glycogen accumulation after inactivation of myostatin in cardiomyocytes. Our results uncover an important role of myostatin in the heart for maintaining cardiac energy homeostasis and preventing cardiac hypertrophy. © 2014 American Heart Association, Inc.

Preparing Children for Heart Surgery

MedlinePlus

... Physical Activity Recommendations for Heart Health • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

High-Resolution Strain Analysis of the Human Heart with Fast-DENSE

NASA Astrophysics Data System (ADS)

Aletras, Anthony H.; Balaban, Robert S.; Wen, Han

1999-09-01

Single breath-hold displacement data from the human heart were acquired with fast-DENSE (fast displacement encoding with stimulated echoes) during systolic contraction at 2.5 × 2.5 mm in-plane resolution. Encoding strengths of 0.86-1.60 mm/π were utilized in order to extend the dynamic range of the phase measurements and minimize effects of physiologic and instrument noise. The noise level in strain measurements for both contraction and dilation corresponded to a strain value of 2.8%. In the human heart, strain analysis has sufficient resolution to reveal transmural variation across the left ventricular wall. Data processing required minimal user intervention and provided a rapid quantitative feedback. The intrinsic temporal integration of fast-DENSE achieves high accuracy at the expense of temporal resolution.

Air travel and adults with cyanotic congenital heart disease.

PubMed

Harinck, E; Hutter, P A; Hoorntje, T M; Simons, M; Benatar, A A; Fischer, J C; de Bruijn, D; Meijboom, E J

1996-01-15

Concern has been expressed that a reduction of partial oxygen pressure during flight in commercial aircraft may induce dangerous hypoxemia in patients with cyanotic congenital heart disease. To evaluate the validity of this concern, the transcutaneous SaO2 was measured in 12 adults with this type of heart disease and 27 control subjects during simulated commercial flights of 1.5 and 7 hours in a hypobaric chamber. Ten of those patients and 6 control subjects also were evaluated during two actual flights of approximately 2.5 hours in a DC-10 and an A-310, respectively. During the prolonged simulated and actual flights, the capillary blood pH, gases, and lactic acid were analyzed in the patients and during one of the actual flights also in the control subjects. During the simulated flights the SaO2 was at all times lower in the patients than in the control subjects. However, the maximal mean actual percentage decrease, as compared with sea level values, did not exceed 8.8% in either patients or control subjects. During the actual flights, this maximal decrease in the patients was 6%. In-flight reduction of the capillary PO2 was considerable in the control subjects but not in the patients. It is our hypothesis that the lack of a significant decrease of the PO2 in the patients might possibly be due to a high concentration of 2.3 diphosphoglycerate in the red cells. The flights had no influence on the capillary blood pH, PCO2, bicarbonate, or lactic acid levels in either patients or control subjects. Atmospheric pressure changes during commercial air travel do not appear to be detrimental to patients with cyanotic congenital heart disease.

Design and Implementation of a Prospective Adult Congenital Heart Disease Biobank.

PubMed

Opotowsky, Alexander R; Loukas, Brittani; Ellervik, Christina; Moko, Lilamarie E; Singh, Michael N; Landzberg, Elizabeth I; Rimm, Eric B; Landzberg, Michael J

2016-11-01

Adults with congenital heart disease (ACHD) comprise a growing, increasingly complex population. The Boston Adult Congenital Heart Disease Biobank is a program for the collection and storage of biospecimens to provide a sustainable resource for scientific biomarker investigation in ACHD. We describe a protocol to collect, process, and store biospecimens for ACHD or associated diagnoses developed based on existing literature and consultation with cardiovascular biomarker epidemiologists. The protocol involves collecting urine and ∼48.5 mL of blood. A subset of the blood and urine undergoes immediate clinically relevant testing. The remaining biospecimens are processed soon after collection and stored at -80°C as aliquots of ethylenediaminetetraacetic acid (EDTA) and lithium heparin plasma, serum, red cell and buffy coat pellet, and urine supernatant. Including tubes with diverse anticoagulant and clot accelerator contents will enable flexible downstream use. Demographic and clinical data are entered into a database; data on biospecimen collection, processing, and storage are managed by an enterprise laboratory information management system. Since implementation in 2012, we have enrolled more than 650 unique participants (aged 18-80 years, 53.3% women); the Biobank contains over 11,000 biospecimen aliquots. The most common primary CHD diagnoses are single ventricle status-post Fontan procedure (18.8%), repaired tetralogy of Fallot with pulmonary stenosis or atresia (17.6%), and left-sided obstructive lesions (17.5%). We describe the design and implementation of biospecimen collection, handling, and storage protocols with multiple levels of quality assurance. These protocols are feasible and reflect the size and goals of the Boston ACHD Biobank. © The Author(s) 2016.

Hippo pathway deficiency reverses systolic heart failure after infarction.

PubMed

Leach, John P; Heallen, Todd; Zhang, Min; Rahmani, Mahdis; Morikawa, Yuka; Hill, Matthew C; Segura, Ana; Willerson, James T; Martin, James F

2017-10-12

Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.

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

PubMed Central

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

2009-01-01

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

Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

PubMed Central

Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

2010-01-01

Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not

Maturity and adherence in adolescent and young adult heart recipients.

PubMed

Stilley, Carol S; Lawrence, Kathy; Bender, Ann; Olshansky, Ellen; Webber, Steven A; Dew, Mary Amanda

2006-05-01

Pediatric transplant (txp) teams note high rates of non-adherence and risky behaviors linked to morbidity and mortality among adolescent and young adult recipients. Clinicians and parents alike report symptoms of social immaturity and failure to appreciate consequences of risky behavior; relationships between the two have not been studied in this population. This two-phase mixed method study examined adherence, high-risk behaviors, and maturity in a sample of 27 heart recipients, aged 15-31, who underwent transplantation in childhood or adolescence at Children's Hospital of Pittsburgh. All subjects completed a projective ego development measure and a questionnaire about adherence to the post-txp regimen. Nine recipients, purposely selected for good or poor adherence according to criteria determined by the transplant team and matched on age, participated in phase 2 qualitative interviews and mood assessments. Sixty-three percent of the phase 1 sample missed medications, 67% missed appointments, 11% smoked, 37% had difficulty with diet, 89% exercised infrequently, 33% had tattoos, 26% had more than two body piercings, and 11% used street drugs. Six themes and a core construct of maturity were identified with qualitative methodology. Poor adherers were less mature on every theme and consistently scored at a less mature level on the projective measure of ego development. Chronological age was not related to the level of maturity in qualitative or projective data. Most interview subjects reported high levels of anxiety, and two reported clinically significant levels of depression and anger; mood was not related to adherence. Non-adherence and high-risk behaviors are prevalent among adolescent and young adult heart recipients. Level of maturity appears to be associated with ability to adhere to the treatment regimen and avoid high-risk behaviors.

Echocardiographic image of an active human heart

NASA Technical Reports Server (NTRS)

2003-01-01

Echocardiographic images provide quick, safe images of the heart as it beats. While a state-of-the art echocardiograph unit is part of the Human Research Facility on International Space Station, quick transmission of images and data to Earth is a challenge. NASA is developing techniques to improve the echocardiography available to diagnose sick astronauts as well as study the long-term effects of space travel on their health. Echocardiography uses ultrasound, generated in a sensor head placed against the patient's chest, to produce images of the structure of the heart walls and valves. However, ultrasonic imaging creates an enormous volume of data, up to 220 million bits per second. This can challenge ISS communications as well as Earth-based providers. Compressing data for rapid transmission back to Earth can degrade the quality of the images. Researchers at the Cleveland Clinic Foundation are working with NASA to develop compression techniques that meet imaging standards now used on the Internet and by the medical community, and that ensure that physicians receive quality diagnostic images.

Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.

PubMed

Pastore, Robert L; Brooks, Judith T; Carbone, John W

2015-06-01

Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasma urotensin in human systolic heart failure.

PubMed

Ng, Leong L; Loke, Ian; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

2002-12-03

Human urotensin II (UTN) has potent vasoactive and cardiostimulatory effects, acting on the G protein-linked receptor GPR14. Myocardial UTN expression is upregulated in heart failure, and UTN stimulates myocardial expression of the natriuretic peptides. We investigated plasma UTN levels in heart failure (HF; left ventricular systolic dysfunction) in comparison with plasma N-terminal pro-brain natriuretic peptide (N-BNP) levels. N-BNP and UTN were measured in plasma from 126 patients with HF and 220 age- and sex-matched controls. Both peptides were elevated in plasma of HF patients and were correlated (r(s)=0.35, P<0.001). In contrast to N-BNP, there was no relationship of plasma UTN with New York Heart Association (NYHA) class. Although plasma N-BNP showed a positive relationship with age and female sex, there was no such age-dependent change in plasma UTN, and control women had lower levels compared with control men. Receiver operating characteristic curves for the diagnosis of HF had areas of 0.90 and 0.86 for N-BNP and UTN, respectively (P<0.001 for both). Receiver operating characteristic curve area for diagnosis of NYHA class I HF with UTN was better than that with N-BNP. Plasma UTN is elevated in HF, which suggests a pathophysiological role for this peptide. Plasma UTN may be a useful alternative to N-BNP in the diagnosis of HF, inasmuch as its levels are elevated irrespective of age, sex, or NYHA class.

Personal growth, symptoms, and uncertainty in community-residing adults with heart failure.

PubMed

Overbaugh, Kristen J; Parshall, Mark B

Personal growth has not been studied extensively in heart failure (HF). To characterize personal growth in HF and its relationships with symptom burden, uncertainty, and demographic and clinical factors. Associations among personal growth, uncertainty, symptom burden, and clinical and demographic variables were examined in adult outpatients with HF using bivariate correlations and multiple regressions. Participants (N = 103; 76% male, mean age = 74 years, 97% New York Heart Association classes II and III) reported moderate levels of personal growth, uncertainty, and symptom burden. Personal growth was weakly correlated with age and symptom burden but not with other study variables. In a regression model, age, sex, ethnicity, disease severity, time since diagnosis, symptom burden, and uncertainty were not significant independent correlates of personal growth. Community-residing patients with HF report moderate personal growth that is not explained by uncertainty, symptom burden, or demographic and clinical variables. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-concepts of exercise in frail older adults with heart failure: a literature review.

PubMed

Xie, Boqin; Arslanian-Engoren, Cynthia

2015-01-01

The co-occurrence of frailty and heart failure (HF) in older adults (65 years or older) can adversely affect the ability to engage in self-care management behaviors, which may alter self-concepts and decrease quality of life. Little is known about how frailty and HF influence older adults' self-concepts or how these self-concepts affect exercise behaviors. Therefore, the aims of this literature review were to identify the self-concepts of older frail adults with HF and to identify how these self-concepts affect their exercise behaviors. Guided by the schema model of self-concept, publications before April 2013 that examined the impact of the self-concepts of older adults with HF and/or frailty on exercise behavior were reviewed. As a result, 6 articles were included. Three of the 6 articles focused on frailty, and 3 of the 6 articles focused on HF. However, no study was found that specifically examined the self-concepts of frail older adults with HF. The self-concepts of older adults with HF and/or frailty are multifaceted and include both cognitive resources (facilitating exercise) and cognitive liabilities (hindering exercise). Studies are needed to determine how the co-occurrence of frailty and HF impact self-concepts and exercise behaviors in older adults.

Human Adult Neurogenesis: Evidence and Remaining Questions.

PubMed

Kempermann, Gerd; Gage, Fred H; Aigner, Ludwig; Song, Hongjun; Curtis, Maurice A; Thuret, Sandrine; Kuhn, H Georg; Jessberger, Sebastian; Frankland, Paul W; Cameron, Heather A; Gould, Elizabeth; Hen, Rene; Abrous, D Nora; Toni, Nicolas; Schinder, Alejandro F; Zhao, Xinyu; Lucassen, Paul J; Frisén, Jonas

2018-04-18

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-term follow-up of implantable cardioverter-defibrillators in adult congenital heart disease patients: indications and outcomes.

PubMed

Santharam, Sandhya; Hudsmith, Lucy; Thorne, Sara; Clift, Paul; Marshall, Howard; De Bono, Joseph

2017-03-01

Ventricular arrhythmias are a major cause of mortality in adult congenital heart disease (ACHD) patients. The European Society of Cardiology guidelines state that implantable cardioverter-defibrillators (ICD) should be considered in patients with congenital heart disease following spontaneous sustained ventricular tachycardia (VT) or cardiac arrest and in patients at presumed high risk. This study sought to analyse the circumstances in which ACHD patients received ICD and to assess outcomes of ICD implantation, including therapies delivered and the rate of complications. A retrospective review was performed of all adult patients with congenital heart disease undergoing ICD implant between 2000 and 2014, in a large quaternary referral centre with over 4000 adults with congenital heart disease under active follow-up. Demographics: 42 patients with congenital heart disease had ICD implants: 55% male; age range 21-71 years and mean age 45 years. Mean age at implantation of ICD was 41 years. Mean follow-up was 5 years. Diagnosis: 50% of patients had repaired tetralogy of Fallot (TOF). Twelve per cent of patients had repaired transposition of the great arteries. Reason for ICD: 15 patients (35.7%) received ICD after sustained VT. Eleven patients (26.2%) received ICD after cardiac arrest. Sixteen (38%) had ICD implanted as primary prophylaxis. Outcome: Since implantation, six patients received an appropriate full-output shock for VT from ICD. Nineteen (45%) patients suffered significant complications (inappropriate shocks 11, inappropriate anti-tachycardia pacing resulting in VF 1, infection requiring extraction 3, lead abnormalities 3, and pneumothorax 1). Equal proportions of primary and secondary prevention patients received appropriate shocks. Most patients had ICD for secondary prevention (62%), and the majority had repaired TOF. There was a 2.9% annual appropriate shock rate. However, there was a high incidence of complications with more than a third suffering a

Have you got any cholesterol? Adults' views of human nutrition

NASA Astrophysics Data System (ADS)

Schibeci, Renato; Wong, Khoon Yoong

1994-12-01

The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

PubMed

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

NASA Technical Reports Server (NTRS)

Alexander, Tiffaney Miller

2017-01-01

Research results have shown that more than half of aviation, aerospace and aeronautics mishaps incidents are attributed to human error. As a part of Safety within space exploration ground processing operations, the identification and/or classification of underlying contributors and causes of human error must be identified, in order to manage human error. This research provides a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

NASA Technical Reports Server (NTRS)

Alexander, Tiffaney Miller

2017-01-01

Research results have shown that more than half of aviation, aerospace and aeronautics mishaps/incidents are attributed to human error. As a part of Safety within space exploration ground processing operations, the identification and/or classification of underlying contributors and causes of human error must be identified, in order to manage human error. This research provides a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

NASA Technical Reports Server (NTRS)

Alexander, Tiffaney Miller

2017-01-01

Research results have shown that more than half of aviation, aerospace and aeronautics mishaps incidents are attributed to human error. As a part of Quality within space exploration ground processing operations, the identification and or classification of underlying contributors and causes of human error must be identified, in order to manage human error.This presentation will provide a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

Effects of severe caloric restriction from birth on the hearts of adult rats.

PubMed

Melo, Dirceu Sousa; Riul, Tania Regina; Esteves, Elizabeth Adriana; Moraes, Patrícia Lanza; Ferreira, Fernanda Oliveira; Gavioli, Mariana; Alves, Márcia Netto Magalhães; Almeida, Pedro William Machado; Guatimosim, Silvia; Ferreira, Anderson José; Dias Peixoto, Marco Fabricio

2013-08-01

There has been increasing evidence suggesting that a severe caloric restriction (SCR) (above 40%) has beneficial effects on the hearts of rats. However, most of the reports have focused on the effects of SCR that started in adulthood. We investigated the consequences of SCR on the hearts of rats subjected to SCR since birth (CR50). From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Thereafter, a maximal aerobic test was performed to indirectly evaluate global cardiovascular function. Indices of contractility (+dT/dt) and relaxation (-dT/dt) were analyzed in isolated heart preparation, and cardiomyocyte diameter, number, density, and myocardium collagen content were obtained through histologic analysis. Ventricular myocytes were isolated, using standard methods to evaluate phosphorylated AKT levels, and Ca(2+) handling was evaluated with a combination of Western blot analysis, intracellular Ca(2+) imaging, and confocal microscopy. CR50 rats exhibited increased aerobic performance and cardiac function, as shown by the increase in ±dT/dt. Despite the smaller cardiomyocyte diameter, CR50 rats had an increased heart-body weight ratio, increased cardiomyocyte density and number, and similar levels of myocardium collagen content, compared with AL rats. AKT was hyperphosphorylated in cardiomyocytes from CR50 rats, and there were no significant differences in Ca(2+) transient and SERCA2 levels in cardiomyocytes between CR50 and AL rats. Collectively, these observations reveal the beneficial effects of a 50% caloric restriction on the hearts of adult rats restricted since birth, which might involve cardiomyocyte AKT signaling.

A PKM2 signature in the failing heart

PubMed Central

Rees, Meredith L.; Subramaniam, Janani; Li, Yuanteng; Hamilton, Dale J.; Frazier, O. Howard; Taegtmeyer, Heinrich

2015-01-01

A salient feature of the failing heart is metabolic remodeling towards predominant glucose metabolism and activation of the fetal gene program. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor used for the treatment of highly vascularized tumors. In diabetic patients, sunitinib significantly decreases blood glucose. However, a considerable proportion of sunitinib-treated patients develop cardiac dysfunction or failure. We asked whether sunitinib treatment results in shift towards glycolysis in the heart. Glucose uptake by the heart was increased fivefold in mice treated with sunitinib. Transcript analysis by qPCR revealed an induction of genes associated with glycolysis and reactivation of the fetal gene program. Additionally, we observed a shift in the enzyme pyruvate kinase from the adult M1 (PKM1) isoform to the fetal M2 (PKM2) isoform, a hallmark of the Warburg Effect. This novel observation led us to examine whether a similar shift occurs in human heart failure. Examination of tissue from patients with heart failure similarly displayed an induction of PKM2. Moreover, this phenomenon was partially reversed following mechanical unloading. We propose that pyruvate kinase isoform switching represents a novel feature of the fetal gene program in the failing heart. PMID:25735978

The Adult Congenital and Pediatric Cardiology Section: increasing the opportunities for the congenital heart disease community within the American College of Cardiology.

PubMed

Martin, Gerard R; Mitchell, Stephanie; Beekman, Robert H; Feinstein, Jeffrey A; Jenkins, Kathy J; Landzberg, Michael; Webb, Gary

2012-01-03

The Adult Congenital and Pediatric Cardiology (AC/PC) Section was established to develop a clear voice within the American College of Cardiology and address the myriad issues facing the congenital heart disease profession. The Section is governed by the AC/PC Council, which includes pediatric cardiologists, adult congenital cardiologists, a cardiac care associate, and a fellow-in-training member. The Council is responsible for bidirectional communication between the College's Board of Trustees and the AC/PC Section members. Since its founding in 2004, Section objectives have been defined by the College's mission: to advocate for quality cardiovascular care through education, research promotion, and the development and application of standards and guidelines and to influence health care policy. The pillars of the College-advocacy, quality, education, and member engagement-serve as the defining template for the Section's strategy. The Section has developed work groups in advocacy, clinical practice, education and training, quality, and publications. A separate leadership group has been developed for adult congenital heart disease. Work groups are open to all Section members. Recognition of the importance of lifelong care in congenital heart disease led Section leaders to incorporate pediatric cardiology and adult congenital heart disease content into each of the work groups. There are more than 1,200 Section members, with nearly 400 members actively contributing to Section activities. This article outlines Section efforts to date and highlights significant successes to date. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Experiences and Outcomes of Transition from Pediatric to Adult Health Care Services for Young People with Congenital Heart Disease: A Systematic Review.

PubMed

Heery, Emily; Sheehan, Aisling M; While, Alison E; Coyne, Imelda

2015-01-01

This review synthesizes the empirical literature on outcomes and experiences of transfer and transition from pediatric to adult care for young people with congenital heart disease. A systematic review of papers published between January 2001 and May 2013 that examined outcomes or experiences of transfer and transition among young people with congenital heart disease was conducted. Data were extracted by two independent reviewers with the outcomes data combined using narrative synthesis and the experiences data integrated using thematic synthesis. Thirteen papers were included in the review: six reported outcomes following transfer, six reported experiences of transfer and transition, and one reported both outcomes and experiences. The review data indicate that high proportions of young people were lost to follow-up or experienced long gaps in care after leaving pediatric cardiology. Factors that protected against loss to follow-up or lapse in care included: beliefs that specialized adult care was necessary; poorer health status; attendance at pediatric appointments without parents; and pediatric referral to an adult congenital heart disease center. Data on experiences highlighted that many young people were unconcerned about transition, but lacked knowledge about their condition and were insufficiently prepared for transfer. In terms of adult services, many young people desired continuity in the quality of care, youth-oriented facilities, a personalized approach, and for their parents to remain involved in their care, but in a secondary, supportive capacity. In conclusion, the high proportions of young people lost to follow-up highlight the need for formal transition programs, which ensure a planned and coordinated transfer. Patients with congenital heart disease need education throughout adolescence about the implications of their condition, the differences between pediatric and adult services, and self-care management. © 2015 Wiley Periodicals, Inc.

A pilot study of expenditures on, and utilization of resources in, health care in adults with congenital heart disease.

PubMed

Moons, P; Siebens, K; De Geest, S; Abraham, I; Budts, W; Gewillig, M

2001-05-01

Congenital cardiac disease may be a chronic condition, necessitating life-long follow-up for a substantial proportion of the patients. Such patients, therefore, are often presumed to be high users of resources for health care. Information on utilization of resources in adults with congenital heart disease, however, is scarce. This retrospective pilot study, performed in Belgium, investigated 192 adults with congenital heart disease to measure the annual expenditures and utilization of health care and compared the findings with data from the general population. We also sought to explore demographic and clinical parameters as predictors for the expenditures. Hospitalization was documented in 20.3% of the patients, with a median length of stay of 5 days. The overall payment by health insurance associations in 1997 was 1794.5 ECU per patient, while patients paid on average 189.5 ECU out-of-pocket. For medication, the average reimbursement and out-of-pocket expenses were estimated at 78 ECU and 20 ECU, respectively. Expenditures for patients with congenital heart disease were considerably higher than the age and gender-corrected expenditures for the general population (411.7 ECU), though this difference was accounted for by only one-eighth of the cohort of those with congenital heart disease. In general, higher expenditures were associated with abnormal left ventricular end-diastolic diameter, female gender, functional impairment and higher age, although the explained variance was limited. Our study has provided pilot data on the economic outcomes for patients with congenital heart diseases. We have identified parameters that could predict expenditure, but which will have to be examined in future research. This is needed to develop guidelines for health insurance for those with congenital heart diseases.

Prospective Study of Adenosine on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After Heart Transplantation.

PubMed

Flyer, Jonathan N; Zuckerman, Warren A; Richmond, Marc E; Anderson, Brett R; Mendelsberg, Tamar G; McAllister, Jennie M; Liberman, Leonardo; Addonizio, Linda J; Silver, Eric S

2017-06-20

Supraventricular tachycardia is common after heart transplantation. Adenosine, the standard therapy for treating supraventricular tachycardia in children and adults without transplantation, is relatively contraindicated after transplantation because of a presumed risk of prolonged atrioventricular block in denervated hearts. This study tested whether adenosine caused prolonged asystole after transplantation and if it was effective in blocking atrioventricular nodal conduction in these patients. This was a single-center prospective clinical study including healthy heart transplant recipients 6 months to 25 years of age presenting for routine cardiac catheterization during 2015 to 2016. After catheterization, a transvenous pacing catheter was placed and adenosine was given following a dose-escalation protocol until atrioventricular block was achieved. The incidence of clinically significant asystole (≥12 seconds after adenosine) was quantified. The effects of patient characteristics on adenosine dose required to produce atrioventricular block and duration of effect were also measured. Eighty patients completed adenosine testing. No patient (0%; 95% confidence interval, 0-3) required rescue ventricular pacing. Atrioventricular block was observed in 77 patients (96%; 95% confidence interval, 89-99). The median longest atrioventricular block was 1.9 seconds (interquartile range, 1.4-3.2 seconds), with a mean duration of adenosine effect of 4.3±2.0 seconds. No patient characteristic significantly predicted the adenosine dose to produce atrioventricular block or duration of effect. Results were similar across patient weight categories. Adenosine induces atrioventricular block in healthy pediatric and young adult heart transplant recipients with minimal risk when low initial doses are used (25 μg/kg; 1.5 mg if ≥60 kg) and therapy is gradually escalated. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02462941. © 2017 American Heart Association, Inc.

Rejuvenating the senescent heart

PubMed Central

Nguyen, Nathalie; Sussman, Mark A.

2015-01-01

Purpose of review The purpose of this review is to provide an update on the cardiac stem cell field with an emphasis on aging and to suggest some relevant strategies directed toward rejuvenation of the senescent heart. Recent findings Stem cells were long considered as a fountain of youth and were assumed to be equipped against any form of aging effect. However, it is now clear that stem cells suffer the consequences of aging as well. With the discovery that cardiac stem cells reside in the heart comes the question whether these cells are also impaired upon aging. As cardiac stem cell properties are also altered with age, autologous stem cell-based therapy to treat heart failure will benefit from new improved strategies. Summary With the goal to improve stem cell properties that are impaired upon aging, some strategies are highlighted. Genetic modification of adult human cardiac progenitor cells prior to autologous stem cell-based therapy, delivery of the next generation of stem cells such as CardioChimeras and CardioClusters, and improvement of the myocardial environment with rejuvenating factors constitute some of the possibilities and are discussed in more detail in this review. PMID:25760821

Illness Representations, Treatment Beliefs, Medication Adherence, and 30-Day Hospital Readmission in Adults With Chronic Heart Failure: A Prospective Correlational Study.

PubMed

Turrise, Stephanie

2016-01-01

An estimated 5.1 million Americans have chronic heart failure, yet despite advances in its treatment, there has been no improvement in hospital readmissions among aging adult patients with chronic heart failure. The purpose of this study is to investigate the relationships among illness representations, treatment beliefs, medication adherence, and 30-day hospital readmission for heart failure exacerbation in aging adults with chronic heart failure. Using a prospective, correlational design, 96 older adults with a primary or secondary diagnosis of heart failure discharged to home from a hospital in the Southeastern United States participated in telephone surveys and follow-up telephone calls. Data analysis included correlation and logistic regression analyses. Participants were highly adherent to their medications. Individuals who did not believe their treatment was effective in controlling their HF were readmitted within 30 days of hospital discharge for HF exacerbation; that is, treatment control was inversely related to 30-day hospital readmission. In post hoc analyses, personal control was inversely related to dichotomized medication adherence and necessity-concern differential was directly related to dichotomized medication adherence. The necessity-concern differential, or the belief that medication necessity outweighed the concerns they had about their medicines, was a significant predictor of medication adherence. Nurses can use these study findings to help identify individuals who may be at risk of being nonadherent to their medications and hospital readmission. Recommendations for future research include replication with multiple sites, the addition of objective measures of medication adherence, investigation of both the cognitive and emotional pathways, and qualitative exploration of personal control in the context of medication adherence in HF.

Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells.

PubMed

Li, Ronald A; Keung, Wendy; Cashman, Timothy J; Backeris, Peter C; Johnson, Bryce V; Bardot, Evan S; Wong, Andy O T; Chan, Patrick K W; Chan, Camie W Y; Costa, Kevin D

2018-05-01

Tissue engineers and stem cell biologists have made exciting progress toward creating simplified models of human heart muscles or aligned monolayers to help bridge a longstanding gap between experimental animals and clinical trials. However, no existing human in vitro systems provide the direct measures of cardiac performance as a pump. Here, we developed a next-generation in vitro biomimetic model of pumping human heart chamber, and demonstrated its capability for pharmaceutical testing. From human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCM) embedded in collagen-based extracellular matrix hydrogel, we engineered a three-dimensional (3D) electro-mechanically coupled, fluid-ejecting miniature human ventricle-like cardiac organoid chamber (hvCOC). Structural characterization showed organized sarcomeres with myofibrillar microstructures. Transcript and RNA-seq analyses revealed upregulation of key Ca 2+ -handling, ion channel, and cardiac-specific proteins in hvCOC compared to lower-order 2D and 3D cultures of the same constituent cells. Clinically-important, physiologically complex contractile parameters such as ejection fraction, developed pressure, and stroke work, as well as electrophysiological properties including action potential and conduction velocity were measured: hvCOC displayed key molecular and physiological characteristics of the native ventricle, and showed expected mechanical and electrophysiological responses to a range of pharmacological interventions (including positive and negative inotropes). We conclude that such "human-heart-in-a-jar" technology could facilitate the drug discovery process by providing human-specific preclinical data during early stage drug development. Copyright © 2018. Published by Elsevier Ltd.

Purification of cardiac myocytes from human heart biopsies for gene expression analysis.

PubMed

Kosloski, L M; Bales, I K; Allen, K B; Walker, B L; Borkon, A M; Stuart, R S; Pak, A F; Wacker, M J

2009-09-01

The collection of gene expression data from human heart biopsies is important for understanding the cellular mechanisms of arrhythmias and diseases such as cardiac hypertrophy and heart failure. Many clinical and basic research laboratories conduct gene expression analysis using RNA from whole cardiac biopsies. This allows for the analysis of global changes in gene expression in areas of the heart, while eliminating the need for more complex and technically difficult single-cell isolation procedures (such as flow cytometry, laser capture microdissection, etc.) that require expensive equipment and specialized training. The abundance of fibroblasts and other cell types in whole biopsies, however, can complicate gene expression analysis and the interpretation of results. Therefore, we have designed a technique to quickly and easily purify cardiac myocytes from whole cardiac biopsies for RNA extraction. Human heart tissue samples were collected, and our purification method was compared with the standard nonpurification method. Cell imaging using acridine orange staining of the purified sample demonstrated that >98% of total RNA was contained within identifiable cardiac myocytes. Real-time RT-PCR was performed comparing nonpurified and purified samples for the expression of troponin T (myocyte marker), vimentin (fibroblast marker), and alpha-smooth muscle actin (smooth muscle marker). Troponin T expression was significantly increased, and vimentin and alpha-smooth muscle actin were significantly decreased in the purified sample (n = 8; P < 0.05). Extracted RNA was analyzed during each step of the purification, and no significant degradation occurred. These results demonstrate that this isolation method yields a more purified cardiac myocyte RNA sample suitable for downstream applications, such as real-time RT-PCR, and allows for more accurate gene expression changes in cardiac myocytes from heart biopsies.

Illness perceptions in adult congenital heart disease: A multi-center international study.

PubMed

Rassart, Jessica; Apers, Silke; Kovacs, Adrienne H; Moons, Philip; Thomet, Corina; Budts, Werner; Enomoto, Junko; Sluman, Maayke A; Wang, Jou-Kou; Jackson, Jamie L; Khairy, Paul; Cook, Stephen C; Subramanyan, Raghavan; Alday, Luis; Eriksen, Katrine; Dellborg, Mikael; Berghammer, Malin; Johansson, Bengt; Rempel, Gwen R; Menahem, Samuel; Caruana, Maryanne; Veldtman, Gruschen; Soufi, Alexandra; Fernandes, Susan M; White, Kamila S; Callus, Edward; Kutty, Shelby; Luyckx, Koen

2017-10-01

Illness perceptions are cognitive frameworks that patients construct to make sense of their illness. Although the importance of these perceptions has been demonstrated in other chronic illness populations, few studies have focused on the illness perceptions of adults with congenital heart disease (CHD). This study examined (1) inter-country variation in illness perceptions, (2) associations between patient characteristics and illness perceptions, and (3) associations between illness perceptions and patient-reported outcomes. Our sample, taken from APPROACH-IS, consisted of 3258 adults with CHD from 15 different countries. Patients completed questionnaires on illness perceptions and patient-reported outcomes (i.e., quality of life, perceived health status, and symptoms of depression and anxiety). Patient characteristics included sex, age, marital status, educational level, employment status, CHD complexity, functional class, and ethnicity. Linear mixed models were applied. The inter-country variation in illness perceptions was generally small, yet patients from different countries differed in the extent to which they perceived their illness as chronic and worried about their illness. Patient characteristics that were linked to illness perceptions were sex, age, employment status, CHD complexity, functional class, and ethnicity. Higher scores on consequences, identity, and emotional representation, as well as lower scores on illness coherence and personal and treatment control, were associated with poorer patient-reported outcomes. This study emphasizes that, in order to gain a deeper understanding of patients' functioning, health-care providers should focus not only on objective indicators of illness severity such as the complexity of the heart defect, but also on subjective illness experiences. Copyright © 2017 Elsevier B.V. All rights reserved.

Educational level and employment status in adults with congenital heart disease.

PubMed

Pfitzer, Constanze; Helm, Paul C; Rosenthal, Lisa-Maria; Walker, Christoph; Ferentzi, Hannah; Bauer, Ulrike M M; Berger, Felix; Schmitt, Katharina R L

2018-01-01

Purpose Through this study we aimed to assess the educational level and employment status of adults with CHD in Germany. Data were acquired from an online survey carried out in 2015 by the German National Register for Congenital Heart Defects. A total of 1458 adults with CHD participated in the survey (response rate: 37.6%). For 1198 participants, detailed medical information, such as main cardiac diagnosis and information from medical reports, was available. Of the participants surveyed (n=1198), 54.5% (n=653) were female, and the mean age was 30 years. The majority of respondents (59.4%) stated that they had high education levels and that they were currently employed (51.1%). Patients with simple CHD had significantly higher levels of education (p<0.001) and were more likely to be employed (p=0.01) than were patients with complex CHD. More than half of the participants had high education levels and the majority were employed. The association between CHD and its severity and individuals' educational attainment should be investigated more closely in future studies.

Pediatric Heart Transplantation: Transitioning to Adult Care (TRANSIT): Baseline Findings.

PubMed

Grady, Kathleen L; Hof, Kathleen Van't; Andrei, Adin-Cristian; Shankel, Tamara; Chinnock, Richard; Miyamoto, Shelley; Ambardekar, Amrut V; Anderson, Allen; Addonizio, Linda; Latif, Farhana; Lefkowitz, Debra; Goldberg, Lee; Hollander, Seth A; Pham, Michael; Weissberg-Benchell, Jill; Cool, Nichole; Yancy, Clyde; Pahl, Elfriede

2018-02-01

Young adult solid organ transplant recipients who transfer from pediatric to adult care experience poor outcomes related to decreased adherence to the medical regimen. Our pilot trial for young adults who had heart transplant (HT) who transfer to adult care tests an intervention focused on increasing HT knowledge, self-management and self-advocacy skills, and enhancing support, as compared to usual care. We report baseline findings between groups regarding (1) patient-level outcomes and (2) components of the intervention. From 3/14 to 9/16, 88 subjects enrolled and randomized to intervention (n = 43) or usual care (n = 45) at six pediatric HT centers. Patient self-report questionnaires and medical records data were collected at baseline, and 3 and 6 months after transfer. For this report, baseline findings (at enrollment and prior to transfer to adult care) were analyzed using Chi-square and t-tests. Level of significance was p < 0.05. Baseline demographics were similar in the intervention and usual care arms: age 21.3 ± 3.2 vs 21.5 ± 3.3 years and female 44% vs 49%, respectively. At baseline, there were no differences between intervention and usual care for use of tacrolimus (70 vs 62%); tacrolimus level (mean ± SD = 6.5 ± 2.3 ng/ml vs 5.6 ± 2.3 ng/ml); average of the within patient standard deviation of the baseline mean tacrolimus levels (1.6 vs 1.3); and adherence to the medical regimen [3.6 ± 0.4 vs 3.5 ± 0.5 (1 = hardly ever to 4 = all of the time)], respectively. At baseline, both groups had a modest amount of HT knowledge, were learning self-management and self-advocacy, and perceived they were adequately supported. Baseline findings indicate that transitioning HT recipients lack essential knowledge about HT and have incomplete self-management and self-advocacy skills.

Establishing human heart chromium, cobalt and vanadium concentrations by inductively coupled plasma mass spectrometry.

PubMed

Day, Patrick L; Eckdahl, Steven J; Maleszewski, Joseph J; Wright, Thomas C; Murray, David L

2017-05-01

Chromium, cobalt, and vanadium are used in metallic joint prosthesis. Case studies have associated elevated heart tissue cobalt concentrations with myocardial injury. To document the long term heart metal ion concentrations, a validated inductively coupled plasma mass spectroscopy (ICP-MS) method was needed. The method utilized a closed-vessel microwave digestion system to digest the samples. An ICP-MS method utilizing Universal Cell Technology was used to determine our target analyte concentrations. Accuracy was verified using reference materials. Precision, sensitivity, recovery and linearity studies were performed. This method was used to establish a reference range for a non-implant containing cohort of 80 autopsy human heart tissues RESULTS: This method demonstrated an analytic measurement range of 0.5-100ng/mL for each element. Accuracy was within ±10% of target value for each element. Within-run precision for each element was below 20% CV. The chromium, vanadium and cobalt concentrations (mean±SD) were 0.1523±0.2157μg/g, 0.0094±0.0211μg/g and 0.1039±0.1305μg/g respectively in 80 non-implant containing human heart tissue samples. This method provides acceptable recovery of the chromium, cobalt and vanadium in heart tissue; allowing assessment of the effects of metallic joint prosthesis on myocardial health. Copyright © 2017 Elsevier GmbH. All rights reserved.

Awareness of lifestyle risk factors for cancer and heart disease among adults in the UK.

PubMed

Sanderson, Saskia C; Waller, Jo; Jarvis, Martin J; Humphries, Steve E; Wardle, Jane

2009-02-01

To examine and compare awareness of lifestyle risk factors for cancer and heart disease in a single UK representative sample. Two open-ended questions about cancer and heart disease risk factors were included in a population-based survey of 1747 adults. Responses were coded for four lifestyles with established links to both diseases: smoking, eating an unhealthy diet, drinking excessive alcohol and physical inactivity. Awareness of lifestyle risk factors was low for both diseases, although higher for heart disease than cancer. The average number identified by respondents was 2.1 (heart disease) and 1.4 (cancer). The strongest predictor was education (both p<0.001). Awareness that physical inactivity is a cancer risk factor was particularly low at 7%. These findings suggest that public awareness of the impact of lifestyle on commonly feared diseases, especially cancer, is low. Unhealthy lifestyles make a significant contribution to ill health and mortality. Increased public awareness of the links between lifestyles and commonly feared diseases might help people understand the potential health consequences of their actions and encourage them to make much-needed lifestyle changes. Efforts are needed to improve public health messages about how lifestyle risk factors impact on the chances of developing these important diseases.

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.

Gender differences in the link between childhood socioeconomic conditions and heart attack risk in adulthood.

PubMed

Hamil-Luker, Jenifer; O'Rand, Angela M

2007-02-01

A growing body of evidence shows that childhood socioeconomic status (SES) is predictive of disease risk in later life, with those from the most disadvantaged backgrounds more likely to experience poor adult-health outcomes. Most of these studies, however are based on middle-aged male populations and pay insufficient attention to the pathways between childhood risks and specific adult disorders. This article examines gender differences in the link between childhood SES and heart attack risk trajectories and the mechanisms by which early environments affect future disease risk. By using methods that model both latent and path-specific influences, we identify heterogeneity in early life conditions and human, social, and health capital in adulthood that contribute to diverse heart attack risk trajectories between and among men and women as they age into their 60s and 70s. We find that key risk factors for heart attack operate differently for men and women. For men, childhood SES does not differentiate those at low, increasing, and high risk for heart attack. In contrast, women who grew up without a father and/or under adverse economic conditions are the most likely to experience elevated risk for heart attack, even after we adjust for the unequal distribution of working and living conditions, social relationships, access to health care, and adult lifestyle behaviors that influence health outcomes.

Adult Education & Human Resource Development: Overlapping and Disparate Fields

ERIC Educational Resources Information Center

Watkins, Karen E.; Marsick, Victoria J.

2014-01-01

Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

Triboelectric Nanogenerator Enabled Body Sensor Network for Self-Powered Human Heart-Rate Monitoring.

PubMed

Lin, Zhiming; Chen, Jun; Li, Xiaoshi; Zhou, Zhihao; Meng, Keyu; Wei, Wei; Yang, Jin; Wang, Zhong Lin

2017-09-26

Heart-rate monitoring plays a critical role in personal healthcare management. A low-cost, noninvasive, and user-friendly heart-rate monitoring system is highly desirable. Here, a self-powered wireless body sensor network (BSN) system is developed for heart-rate monitoring via integration of a downy-structure-based triboelectric nanogenerator (D-TENG), a power management circuit, a heart-rate sensor, a signal processing unit, and Bluetooth module for wireless data transmission. By converting the inertia energy of human walking into electric power, a maximum power of 2.28 mW with total conversion efficiency of 57.9% was delivered at low operation frequency, which is capable of immediately and sustainably driving the highly integrated BSN system. The acquired heart-rate signal by the sensor would be processed in the signal process circuit, sent to an external device via the Bluetooth module, and displayed on a personal cell phone in a real-time manner. Moreover, by combining a TENG-based generator and a TENG-based sensor, an all-TENG-based wireless BSN system was developed, realizing continuous and self-powered heart-rate monitoring. This work presents a potential method for personal heart-rate monitoring, featured as being self-powered, cost-effective, noninvasive, and user-friendly.

Germline stem cells and neo-oogenesis in the adult human ovary.

PubMed

Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

2007-06-01

It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

Burden and Depressive Symptoms Associated with Adult-Child Caregiving for Individuals with Heart Failure

PubMed Central

Zincir, Serkan; Aydin Sunbul, Esra; Oguz, Mustafa; Feriha Cengiz, Fatma; Durmus, Erdal; Kivrak, Tarik; Sari, Ibrahim

2014-01-01

Background. The primary purpose of this study was to investigate adult-child caregiver burden in heart failure (HF) patients. Secondary purpose of the study was to identify the possible influencing factors for caregiver burden and depressive symptoms in a young adult-child caregiver group. Methods. A total of 138 adult-child caregivers and 138 patients with HF participated in this study. Caregivers' burden, depressive symptoms, and anxiety levels were assessed by using Zarit Caregiver Burden Scale (ZCBS), Beck Depression Inventory, and State-Trait Anxiety Inventory, respectively. Results. The mean ZCBS scores of the female caregivers were significantly higher than male caregivers. Approximately one-third of the adult-child caregivers had at least mild depressive symptoms. Caregivers with higher depressive symptoms had higher levels of caregiver burden. There were positive correlations between caregiving time, severity of depressive symptoms, and perceived caregiver burden. There was a negative correlation between education level of caregivers and perceived caregiver burden. Age, socioeconomic level, and marital status of patients were affecting factors for depressive symptoms in caregivers. Among caregiver characteristics, gender, marital status, and ZCBS scores seem to influence the depression in caregivers. Conclusions. The study findings suggest significant levels of burden and depressive symptoms even in adult-child caregivers of HF patients. PMID:25431793

Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

PubMed

Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

2015-09-01

Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

The relationship between human dignity and medication adherence in patients with heart failure.

PubMed

Amininasab, Seyedeh Somayeh; Azimi Lolaty, Hamideh; Moosazadeh, Mahmood; Shafipour, Vida

2017-01-01

Medication adherence is a behavior that is influenced by several factors, and maintaining patients' dignity is an important issue that needs to be considered in the course of treatment . The present study aimed to determine the relationship between human dignity and medication adherence in patients with heart failure. This was a cross-sectional study. A total number of 300 patients with heart failure admitted to the Mazandaran Heart Center, Iran, participated in this study by census. Samples were selected based on inclusion criteria such as an HF diagnosis by a cardiologist for a minimum of 6 months, and taking at least one cardiac medication. Data were collected through demographic, clinical, human dignity, and medication adherence questionnaires over a period of three months in 2016. This study was approved by the Ethics Committee of Mazandaran University of Medical Sciences. Consents were obtained from patients and the medical center, and necessary explanations were given about the confidentiality of information prior to completing the questionnaires. The mean score of medication adherence was 5.82 suggesting low medication adherence among the patients, and the mean score of human dignity was 81.39. There was a negative relationship between medication adherence and threat to human dignity (r = - 0.6, P < 0.001), i.e., the higher the scores of threat, the lower the medication adherence of the patients. After adjusting the effects of potential confounding variables, there still was a correlation between medication adherence and the variables of human dignity and its dimensions. Based on the findings, an increase in patients' dignity can enhance medication adherence, which can theoretically improve patients' health and reduce frequent hospitalization.

S-Nitrosoglutathione Reductase Deficiency Enhances the Proliferative Expansion of Adult Heart Progenitors and Myocytes Post Myocardial Infarction

PubMed Central

Hatzistergos, Konstantinos E; Paulino, Ellena C; Dulce, Raul A; Takeuchi, Lauro M; Bellio, Michael A; Kulandavelu, Shathiyah; Cao, Yenong; Balkan, Wayne; Kanashiro-Takeuchi, Rosemeire M; Hare, Joshua M

2015-01-01

Background Mammalian heart regenerative activity is lost before adulthood but increases after cardiac injury. Cardiac repair mechanisms, which involve both endogenous cardiac stem cells (CSCs) and cardiomyocyte cell-cycle reentry, are inadequate to achieve full recovery after myocardial infarction (MI). Mice deficient in S-nitrosoglutathione reductase (GSNOR−⁄−), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI. Here, we tested the hypothesis that GSNOR activity modulates cardiac cell proliferation in the post-MI adult heart. Methods and Results GSNOR−⁄− and C57Bl6/J (wild-type [WT]) mice were subjected to sham operation (n=3 GSNOR−⁄−; n=3 WT) or MI (n=41 GSNOR−⁄−; n=65 WT). Compared with WT,GSNOR−⁄− mice exhibited improved survival, cardiac performance, and architecture after MI, as demonstrated by higher ejection fraction (P<0.05), lower endocardial volumes (P<0.001), and diminished scar size (P<0.05). In addition, cardiomyocytes from post-MI GSNOR−⁄− hearts exhibited faster calcium decay and sarcomeric relaxation times (P<0.001). Immunophenotypic analysis illustrated that post-MI GSNOR−⁄− hearts demonstrated enhanced neovascularization (P<0.001), c-kit+ CSC abundance (P=0.013), and a ≈3-fold increase in proliferation of adult cardiomyocytes and c-kit+/CD45− CSCs (P<0.0001 and P=0.023, respectively) as measured by using 5-bromodeoxyuridine. Conclusions Loss of GSNOR confers enhanced post-MI cardiac regenerative activity, characterized by enhanced turnover of cardiomyocytes and CSCs. Endogenous denitrosylases exert an inhibitory effect over cardiac repair mechanisms and therefore represents a potential novel therapeutic target. PMID:26178404

Pediatric heart transplantation at adult-specialty centers in the US: a multicenter registry analysis.

PubMed

Duong, Son Q; Yabes, Johnathan G; Teuteberg, Jeffery J; Shellmer, Diana A; Feingold, Brian

2018-05-14

Recent OPTN bylaw revisions mandate US transplant programs have an "approved pediatric component" in order to perform heart transplantation (HT) in patients <18 years old. The impact of this change on adolescents, a group known to be at high-risk for graft loss and nonadherence, is unknown. We studied all US pediatric (age <18 years) HT from 2000-2015 to compare graft survival between centers organized primarily for adult versus pediatric care. Centers were designated as pediatric- or adult-specialty care according to the ratio of pediatric:adult HT performed and minimum age of HT (pediatric-specialty defined as ratio>0.7; adult-specialty ratio<0.05 and minimum age >8 years). In propensity score-matched cohorts we observed no difference in graft loss by center type (median survival: adult 12.4 vs. pediatric 9.2 years, p=0.174). Compared to the matched pediatric cohort, adult-specialty center recipients lived closer to their transplant center (31 vs. 45 miles, p=0.012), and trended toward fewer out-of-state transplants (15 vs. 25%, p=0.082). Our data suggest that select adolescents can achieve similar mid-term graft survival at centers organized primary for adult HT care. Regardless of post-HT setting, the development of care models that demonstrably improve adherence, may be of greatest benefit to improving survival of this high-risk population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Plasma microvesicle analysis identifies microRNA 129-5p as a biomarker of heart failure in univentricular heart disease.

PubMed

Ramachandran, Sweta; Lowenthal, Alexander; Ritner, Carissa; Lowenthal, Shiri; Bernstein, Harold S

2017-01-01

Biomarkers of heart failure in adults have been extensively studied. However, biomarkers to monitor the progression of heart failure in children with univentricular physiology are less well understood. We proposed that as mediators of diverse pathophysiology, miRNAs contained within circulating microvesicles could serve as biomarkers for the presence and progression of heart failure in univentricular patients. To test this, we studied the association of heart failure with elevations in specific miRNAs isolated from circulating microvesicles in a cohort of children with univentricular heart disease and heart failure. We conducted a single site cross-sectional observational study of 71 children aged 1 month-7 years with univentricular heart disease and heart failure. We demonstrated that levels of miR129-5p isolated from plasma microvesicles were inversely related to the degree of clinical heart failure as assessed by Ross score. We then showed that miR129-5p levels are downregulated in HL1 cells and human embryonic stem cell-derived cardiomyocytes exposed to oxidative stress. We demonstrated that bone morphogenetic protein receptor 2, which has been implicated in the development of pulmonary vascular disease, is a target of miR129-5p, and conversely regulated in response to oxidative stress in cell culture. Levels of miR129-5p were inversely related to the degree of clinical heart failure in patients with univentricular heart disease. This study demonstrates that miR129-5p is a sensitive and specific biomarker for heart failure in univentricular heart disease independent of ventricular morphology or stage of palliation. Further study is warranted to understand the targets affected by miR129-5p with the development of heart failure in patients with univentricular physiology.

Adverse remodeling of the electrophysiological response to ischemia-reperfusion in human heart failure is associated with remodeling of metabolic gene expression.

PubMed

Ng, Fu Siong; Holzem, Katherine M; Koppel, Aaron C; Janks, Deborah; Gordon, Fabiana; Wit, Andrew L; Peters, Nicholas S; Efimov, Igor R

2014-10-01

Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute ischemia-reperfusion in heart failure and its potential causes, including the remodeling of metabolic gene expression. We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to ischemia-reperfusion, with greater action potential duration shortening (P<0.001 at 8-minute ischemia; P=0.001 at 12-minute ischemia) and greater conduction slowing during ischemia, delayed recovery of electric excitability after reperfusion (F, 4.8±1.8 versus D, 1.0±0 minutes; P<0.05), and incomplete restoration of action potential duration and conduction velocity early after reperfusion. Expression of 46 metabolic genes was probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. We demonstrate, for the first time in human hearts, that the electrophysiological response to ischemia-reperfusion in heart failure is accelerated during ischemia with slower recovery after reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes. © 2014 American Heart Association, Inc.

Care and Treatment for Congenital Heart Defects

MedlinePlus

... Physical Activity Recommendations for Heart Health • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

Marital History and Survival after a Heart Attack

PubMed Central

Dupre, Matthew E.; Nelson, Alicia

2016-01-01

Heart disease is the leading cause of death in the United States and nearly one million Americans will have a heart attack this year. Although the risks associated with a heart attack are well established, we know surprisingly little about how marital factors contribute to survival in adults afflicted with heart disease. This study uses a life course perspective and longitudinal data from the Health and Retirement Study to examine how various dimensions of marital life influence survival in U.S. older adults who suffered a heart attack (n=2,197). We found that adults who were never married (odds ratio [OR]=1.73), currently divorced (OR=1.70), or widowed (OR=1.34) were at significantly greater risk of dying after a heart attack than adults who were continuously married; and the risks were not uniform over time. We also found that the risk of dying increased by 12% for every additional marital loss and decreased by 7% for every one-tenth increase in the proportion of years married. After accounting for more than a dozen socioeconomic, psychosocial, behavioral, and physiological factors, we found that current marital status remained the most robust indicator of survival following a heart attack. The implications of the findings are discussed in the context of life course inequalities in chronic disease and directions for future research. PMID:27770749

Resetting the epigenome for heart regeneration.

PubMed

Quaife-Ryan, Gregory A; Sim, Choon Boon; Porrello, Enzo R; Hudson, James E

2016-10-01

In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyocytes following modulation of these factors rarely reaches neonatal levels. The inefficient re-induction of proliferation in adult cardiomyocytes may be due to the epigenetic landscape, which drastically changes during cardiac development and maturation. In this review, we provide an overview of the role of epigenetic modifiers in developmental processes related to cardiac regeneration. We propose an epigenetic framework for heart regeneration whereby adult cardiomyocyte identity requires resetting to a neonatal-like state to facilitate cell cycle re-entry and regeneration following cardiac injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Heart dysfunction induced by choline-deficiency in adult rats: the protective role of L-carnitine.

PubMed

Strilakou, Athina A; Lazaris, Andreas C; Perelas, Apostolos I; Mourouzis, Iordanis S; Douzis, Ioannis Ch; Karkalousos, Petros L; Stylianaki, Aikaterini Th; Pantos, Costas I; Liapi, Charis A

2013-06-05

Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes. Copyright © 2013 Elsevier B.V. All rights reserved.

The human female heart incorporates glucose more efficiently than the male heart.

PubMed

Kakinuma, Yoshihiko; Okada, Shoshiro; Nogami, Munenobu; Kumon, Yoshitaka

2013-10-03

Oestrogen is known to play a cardioprotective role in cardiovascular diseases, as demonstrated in a number of animal studies. However, few human studies have investigated sex-based differences with regard to cardiac glucose uptake using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). Therefore, we evaluated healthy male and female subjects who underwent FDG-PET/CT examination to determine whether there was a sex-related difference in cardiac glucose uptake with age. In females, the prevalence of maximal FDG uptake (PET score 2) demonstrated a convex pattern with ageing, and it peaked at age 51-60 years in the females, gradually decreasing to a minimum at age >70 years. In contrast, the prevalence of maximal FDG uptake by age in males was a mirror image of that in females, i.e. it formed a concave pattern with a nadir at 61-70 years, followed by an increase in the prevalence. These findings suggest that female hearts depend more on glucose as an energy substrate as they age, however, efficient glucose uptake is attenuated with increasing age. In contrast, the male heart sustains its glucose uptake capacity at age >70 years. This characteristic sex-based difference in cardiac glucose uptake might be related to the female predominance of Takotsubo cardiomyopathy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mental Health and Pain in Older Adults: Findings from Urban HEART-2.

PubMed

Rashedi, Vahid; Asadi-Lari, Mohsen; Foroughan, Mahshid; Delbari, Ahmad; Fadayevatan, Reza

2017-08-01

Pain is an important component of disability problems, and plays a key role in mental health of older adults. This study aims to investigate the relationship between mental health and pain in older adults of Tehran, Iran. This was a cross-sectional study using data on 5326 older adults aged ≥60 years old from a large population-based survey (Urban HEART-2). A multistage cluster random sampling method was used to select the participants in Tehran, Iran, in 2011. General Health Questionnaire (GHQ-28), pain questionnaire, and socioeconomic questionnaires were used to collect the data. A total of 5326 older adults, 3811 (71.6%) married and 2797 (52.5%) female, were included into the study. The mean age of the participants was 68.92 ± 7.02 years. Mean of GHQ-28 scores in the sample was 51.08 ± 10.94, which indicates of a good level of mental health. The majority of the older adults had knee and back pain (more than 50%). Regardless of the chronicity, time, and the mode of reaction to it, knee and back pain were the highly reported pains among the participants. There was a statistically significant difference between two groups of older adults, with and without pain, in terms of GHQ-28 scores. Multiple regression analysis revealed that there was a relationship between mental health and the following factors: pain in head, shoulder, teeth, upper and lower limbs, education, gender, age, and marital status. Whatever the explanation, the relation of lowered health status to pain in all body parts among older people is considerable. This renders this matter as a top priority in health policy making.

Cardiac re-entry dynamics and self-termination in DT-MRI based model of Human Foetal Heart

NASA Astrophysics Data System (ADS)

Biktasheva, Irina V.; Anderson, Richard A.; Holden, Arun V.; Pervolaraki, Eleftheria; Wen, Fen Cai

2018-02-01

The effect of human foetal heart geometry and anisotropy on anatomy induced drift and self-termination of cardiac re-entry is studied here in MRI based 2D slice and 3D whole heart computer simulations. Isotropic and anisotropic models of 20 weeks of gestational age human foetal heart obtained from 100μm voxel diffusion tensor MRI data sets were used in the computer simulations. The fiber orientation angles of the heart were obtained from the orientation of the DT-MRI primary eigenvectors. In a spatially homogeneous electrophysiological monodomain model with the DT-MRI based heart geometries, cardiac re-entry was initiated at a prescribed location in a 2D slice, and in the 3D whole heart anatomy models. Excitation was described by simplified FitzHugh-Nagumo kinetics. In a slice of the heart, with propagation velocity twice as fast along the fibres than across the fibers, DT-MRI based fiber anisotropy changes the re-entry dynamics from pinned to an anatomical re-entry. In the 3D whole heart models, the fiber anisotropy changes cardiac re-entry dynamics from a persistent re-entry to the re-entry self-termination. The self-termination time depends on the re-entry’s initial position. In all the simulations with the DT-MRI based cardiac geometry, the anisotropy of the myocardial tissue shortens the time to re-entry self-termination several folds. The numerical simulations depend on the validity of the DT-MRI data set used. The ventricular wall showed the characteristic transmural rotation of the helix angle of the developed mammalian heart, while the fiber orientation in the atria was irregular.

Effects of smoking on heart rate at rest and during exercise, and on heart rate recovery, in young adults.

PubMed

Papathanasiou, George; Georgakopoulos, Dimitris; Papageorgiou, Effie; Zerva, Efthimia; Michalis, Lampros; Kalfakakou, Vasiliki; Evangelou, Angelos

2013-01-01

There is an established link between smoking, abnormal heart rate (HR) values, and impaired cardiovascular health in middle-aged or older populations. The purpose of this study was to examine the effects of smoking on resting HR and on HR responses during and after exercise in young adults. A sample of 298 young adults (159 men), aged 20-29 years old, were selected from a large population of health-science students based on health status, body mass index, physical activity, and smoking habit. All subjects underwent a maximal Bruce treadmill test and their HR was recorded during, at peak, and after termination of exercise. Smokers had significantly higher resting HR values than non-smokers. Both female and male smokers showed a significantly slower HR increase during exercise. Female smokers failed to reach their age-predicted maximum HR by 6.0 bpm and males by 3.6 bpm. The actual maximum HR achieved (HRmax) was significantly lower for both female smokers (191.0 bpm vs.198.0 bpm) and male smokers (193.2 bpm vs.199.3 bpm), compared to non-smokers. Heart rate reserve was also significantly lower in female (114.6 bpm vs. 128.1 bpm) and male smokers (120.4 bpm vs. 133.0 bpm). During recovery, the HR decline was significantly attenuated, but only in female smokers. Females had a higher resting HR and showed a higher HR response during sub-maximal exercise compared to males. Smoking was found to affect young smokers' HR, increasing HR at rest, slowing HR increase during exercise and impairing their ability to reach the age-predicted HRmax. In addition, smoking was associated with an attenuated HR decline during recovery, but only in females.

Hopelessness among adults with congenital heart disease: Cause for despair or hope?

PubMed

Eslami, Bahareh; Kovacs, Adrienne H; Moons, Philip; Abbasi, Kyomars; Jackson, Jamie L

2017-03-01

Adults with congenital heart disease (CHD) face unique life courses and challenges that may negatively influence their psychological functioning. The aims of this study were to (1) examine the level of hopelessness among adults with CHD in comparison with non-CHD participants and (2) identify correlates of elevated hopelessness among adults with CHD. We enrolled 347 patients with CHD (18-64years, 52.2% female) and 353 matched (by sex/age) non-CHD persons in this cross-sectional study. Hopelessness was assessed by Beck Hopelessness Scale. Hierarchical multiple logistic regression analyses were performed to explore correlates of elevated hopelessness. The mean total hopelessness score did not significantly differ between the CHD and non-CHD groups. Twenty-eight percent of CHD patients had elevated hopelessness scores. Within the CHD patient sample, regression analyses revealed that being male (odds ratio=2.62), not having children (odds ratio=3.57), being unemployed (odds ratio=2.27), and elevated depressive symptoms (odds ratio=1.21) were significantly associated with hopelessness. Regular physical activity (odds ratio=0.36) emerged as a protective factor and all CHD disease parameters were unrelated to hopelessness. The final model explained 43% of the variance in hopelessness. Adult CHD teams are encouraged to continue to explore strategies to support patients to live as rich and full as lives as possible by pursuing relationships, employment and physical activity, as well as managing depression and hopelessness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mechanical signaling coordinates the embryonic heart

NASA Astrophysics Data System (ADS)

Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea

The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.

Successful support of biventricular heart failure patients by new EXCOR® Adult pumps with bileaflet valves: a prospective study.

PubMed

Schmack, Bastian; Weymann, Alexander; Ruschitzka, Frank; Autschbach, Rüdiger; Raake, Philip W; Jurrmann, Nadine; Menon, Ares K; Karck, Matthias; Wilhelm, Markus J; Ruhparwar, Arjang

2018-05-01

The Berlin Heart EXCOR ® Adult biventricular assist device (BiVAD) is an approved mechanical circulatory support for patients with end-stage biventricular heart failure. In this prospective post-market clinical follow-up study, we present the first clinical experience of the new EXCOR ® Adult pump with bileaflet (BL) valves in Europe. After CE-mark approval in August 2014, a total of 12 patients were enrolled with a mean age of 44 years ± 11 (range 21-58 years). The majority of patients (n = 11) were in INTERMACS level 1 or 2. Eight patients had a median pre-operative extracorporeal life support (ECLS) of 6 days (range 1-37 days). Primary end point was survival, either to heart transplantation (HTx), recovery or alive at 12 months on device, whichever occurred first. Secondary end point was the number of adverse events throughout EXCOR ® BiVAD support. Median support time up to last follow-up on EXCOR ® BiVAD device was 248 days (range 57-381 days) and patient survival at 1 year was 92%. Half of the EXCOR ® BiVAD patients (n = 6) were transplanted and five patients were still on support at 1 year post-implantation. Complications during EXCOR ® BiVAD support were thoracic bleeding, exit site infection and ischemic cerebrovascular incidents in three cases, respectively. The new EXCOR ® Adult pump with BL provides pulsatile high cardiac output with excellent outcome and successful bridging to HTx, particularly in critically ill patients with INTERMACS level 1 or 2 at the time of implantation.

Heart rate variability alterations in late life depression: A meta-analysis.

PubMed

Brown, Lydia; Karmakar, Chandan; Gray, Richard; Jindal, Ripu; Lim, Terrence; Bryant, Christina

2018-08-01

There is strong evidence for a bi-directional relationship between heart-health and depression in later life, but the physiological mechanisms underlying this relationship remain unclear. Heart rate variability is one promising factor that might help explain this relationship. We present results of a meta-analysis that considers heart rate variability alterations in older adults with depression. Literature search of Embase, PsychInfo and Medline revealed five clinical studies and six observational studies that examined the relationship between heart rate variability and depression in adults with a mean age over 60. These studies were included in this meta-analysis. Heart rate variability was reduced among older adults with clinical depression (N = 550), relative to healthy controls (Hedges' g = -0.334, 95%CI [-0.579, -0.090], p = .007). When high-frequency and low-frequency heart rate variability were investigated separately, only low-frequency heart rate variability was significantly reduced in depressed patients (Hedges' g = -0.626, 95%CI [-1.083, -0.169], p = .007). A similar but weaker pattern of results was found in the observational studies. Most findings remained significant among unmedicated depressed older adults. Evidence of effect-size heterogeneity was found in the clinical studies, indicating the need for more well-designed research in the area. Heart rate variability is reduced among older adults with depression, and this effect is not fully attributable to antidepressant medication use. Specifically, low-frequency heart rate variability may be reduced in depressed older adults. Heart rate variability warrants further attention, as it could help inform research into the prevention and treatment of depression in later life. Copyright © 2018 Elsevier B.V. All rights reserved.

[Stem cells in adults].

PubMed

Borge, O J; Funderud, S

2001-08-30

We present a literature review of the plasticity observed by adult stem cells. We have reviewed the literature regarding stem cells from adults in order to summarise their ability to generate cells of other types than those of the tissue/organ from which they were isolated. Adult stem cells have recently been demonstrated to terminally differentiate into cells of other tissues than those from which they were originally isolated. For example, bone marrow cells have been shown to generate liver, nerve, heart and skeletal muscle cells in addition to their well-known ability to produce blood and mesenchymal cells. Most studies demonstrate a proof-of-principle in animal models; much more research is needed before adult stem cells can be utilised in human medicine. However, the published reports are encouraging and give reasons for a cautious optimism with regard to future clinical use.

Combined effect of whole-body vibration and ambient lighting on human discomfort, heart rate, and reaction time.

PubMed

Monazzam, Mohammad Reza; Shoja, Esmaeil; Zakerian, Seyed Abolfazl; Foroushani, Abbas Rahimi; Shoja, Mohsen; Gharaee, Masoumeh; Asgari, Amin

2018-07-01

This study aimed to investigate the effect of whole-body vibration and ambient lighting, as well as their combined effect on human discomfort, heart rate, and reaction time in laboratory conditions. 44 men were recruited with an average age of 25.4 ± 1.9 years. Each participant was subjected to 12 experimental steps, each step lasting five minutes for four different vibration accelerations in X, Y, and Z axes at a fixed frequency; three different lighting intensities of 50, 500, and 1000 lx were also considered. At each step, a visual computerized reaction test was taken from subjects and their heart rate recorded by pulse oximeter. In addition, the discomfort rate of subjects was measured using Borg scale. Increasing vibration acceleration significantly increased the discomfort rate and heart beat but not the reaction time. Lack of lighting caused more discomfort in the subjects, but there was no significant correlation between lighting intensity with heart rate and reaction time. The results also showed that the combined effect of vibration and lighting had no significant effect on any of the discomfort, heart rate, and reaction time variables. Whole-body vibration is an important factor in the development of human subjective and physiological reactions compared to lighting. Therefore, consideration of the level of vibration to which an individual is exposed in workplaces subject to vibration plays an important role in reducing the level of human discomfort, but its interaction with ambient lighting does not have a significant effect on human subjective and physiological responses.

Human pancreatic polypeptide in children and young adults.

PubMed

Hanukoglu, A; Chalew, S; Kowarski, A A

1990-01-01

Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults.

Concurrent Isolation of 3 Distinct Cardiac Stem Cell Populations From a Single Human Heart Biopsy.

PubMed

Monsanto, Megan M; White, Kevin S; Kim, Taeyong; Wang, Bingyan J; Fisher, Kristina; Ilves, Kelli; Khalafalla, Farid G; Casillas, Alexandria; Broughton, Kathleen; Mohsin, Sadia; Dembitsky, Walter P; Sussman, Mark A

2017-07-07

The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration. Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy. Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm 3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit + cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit - mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit + population is further enriched by selection for a CD133 + endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry. Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients. © 2017 American Heart Association, Inc.

High-resolution analysis of copy number variants in adults with simple-to-moderate congenital heart disease.

PubMed

Zhao, Wei; Niu, Guannan; Shen, Botao; Zheng, Yang; Gong, Fangchao; Wang, Xianfu; Lee, Jiyun; Mulvihill, John J; Chen, Xiaohui; Li, Shibo

2013-12-01

As patients with congenital heart disease (CHD) increasingly survive to childbearing age, it becomes important to understand the genetic origins of CHD. In children, CHD is frequently caused by chromosomal imbalances. We searched for submicroscopic imbalances in adults with CHD focusing on simple-to-moderate phenotypes, without associated dysmorphic features, a group not previously examined. A total of 100 Han Chinese adults with a diverse range of isolated CHD and 65 ethnically matched controls were screened using whole-genome array comparative genomic hybridization. Forty-five large (>100 kb) rare copy number variants (CNVs) were identified in 36/100 patients. These variants were not listed in the Database of Genomic Variants nor found in controls. In three of these genomic imbalances (22q11.2, 18q23, 3q21.3), genes that play an important role in cardiac development were implicated, including CRKL, NFATC1, PLXNA1, the latter has not been associated with human CHD before. This study detected a 0.7 Mb 22q11.2 deletion, which marginally overlapped the common 3 Mb 22q11.2 deletion, in one patient with a perimembranous ventricular septal defect without any extracardiac manifestation. Furthermore, we detected a novel inherited aberration dup (16q23.1). Although a causal relationship with CHD remains to be established, this CNVs profile provides a spectrum of genomic imbalances in this condition, and improves the CNV-phenotype correlations. © 2013 Wiley Periodicals, Inc.

Mechanical Circulatory Support of the Right Ventricle for Adult and Pediatric Patients With Heart Failure.

PubMed

Chopski, Steven G; Murad, Nohra M; Fox, Carson S; Stevens, Randy M; Throckmorton, Amy L

2018-05-10

The clinical implementation of mechanical circulatory assistance for a significantly dysfunctional or failing left ventricle as a bridge-to-transplant or bridge-to-recovery is on the rise. Thousands of patients with left-sided heart failure are readily benefitting from these life-saving technologies, and left ventricular failure often leads to severe right ventricular dysfunction or failure. Right ventricular failure (RVF) has a high rate of mortality caused by the risk of multisystem organ failure and prolonged hospitalization for patients after treatment. The use of a blood pump to support the left ventricle also typically results in an increase in right ventricular preload and may impair right ventricular contractility during left ventricular unloading. Patients with RVF might also suffer from severe pulmonary dysfunction, cardiac defects, congenital heart disease states, or a heterogeneity of cardiophysiologic challenges because of symptomatic congestive heart failure. Thus, the uniqueness and complexity of RVF is emerging as a new domain of significant clinical interest that motivates the development of right ventricular assist devices. In this review, we present the current state-of-the-art for clinically used blood pumps to support adults and pediatric patients with right ventricular dysfunction or failure concomitant with left ventricular failure. New innovative devices specifically for RVF are also highlighted. There continues to be a compelling need for novel treatment options to support patients with significant right heart dysfunction or failure.

Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence

PubMed Central

Gonzalez-Valdes, I.; Hidalgo, I.; Bujarrabal, A.; Lara-Pezzi, E.; Padron-Barthe, L.; Garcia-Pavia, P.; Gómez-del Arco, Pablo; Redondo, J.M.; Ruiz-Cabello, J.M.; Jimenez-Borreguero, L.J.; Enriquez, J.A.; de la Pompa, J.L.; Hidalgo, A.; Gonzalez, S.

2015-01-01

Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16INK4a derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16INK4a levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation. PMID:25751743

Management of supraventricular arrhythmias in adults with congenital heart disease.

PubMed

Wasmer, Kristina; Eckardt, Lars

2016-10-15

Supraventricular arrhythmias are a frequent complication in adults with congenital heart disease (ACHD). The prevalence increases with time since surgery, complexity of the underlying defect, type of repair and older age at surgery. Arrhythmias are the most frequent reason for hospital admission and along with heart failure the leading cause of death. The arrhythmia-associated increase in morbidity and mortality makes their management a key task in patients with ACHD. Intra-atrial re-entry is the most frequent arrhythmia mechanism. Less common arrhythmia mechanisms are supraventricular tachycardias in the presence of an accessory pathway, atrioventricular nodal re-entrant tachycardia or focal tachycardias. Patient management includes stroke prevention, acute termination and prevention of arrhythmia recurrence. Acute treatment depends on patients' symptoms. In cases of haemodynamic instability, immediate cardioversion is warranted. For stable patients, acute treatment includes rate control and termination by antiarrhythmic drugs or electrical cardioversion. Following a symptomatic arrhythmia, catheter ablation or treatment with antiarrhythmic drugs is recommended to prevent recurrences. Advances in mapping and ablation technology are now associated with high success rates of catheter ablation. In patients with a complex substrate recurrence rates of 50% remain high. However, in the presence of side effects and complications associated with long-term antiarrhythmic drug therapy, redo procedures are encouraged by current guidelines. 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/

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

PubMed

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

2018-06-01

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

Marital history and survival after a heart attack.

PubMed

Dupre, Matthew E; Nelson, Alicia

2016-12-01

Heart disease is the leading cause of death in the United States and nearly one million Americans will have a heart attack this year. Although the risks associated with a heart attack are well established, we know surprisingly little about how marital factors contribute to survival in adults afflicted with heart disease. This study uses a life course perspective and longitudinal data from the Health and Retirement Study to examine how various dimensions of marital life influence survival in U.S. older adults who suffered a heart attack (n = 2197). We found that adults who were never married (odds ratio [OR] = 1.73), currently divorced (OR = 1.70), or widowed (OR = 1.34) were at significantly greater risk of dying after a heart attack than adults who were continuously married; and the risks were not uniform over time. We also found that the risk of dying increased by 12% for every additional marital loss and decreased by 7% for every one-tenth increase in the proportion of years married. After accounting for more than a dozen socioeconomic, psychosocial, behavioral, and physiological factors, we found that current marital status remained the most robust indicator of survival following a heart attack. The implications of the findings are discussed in the context of life course inequalities in chronic disease and directions for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Common multifractality in the heart rate variability and brain activity of healthy humans

NASA Astrophysics Data System (ADS)

Lin, D. C.; Sharif, A.

2010-06-01

The influence from the central nervous system on the human multifractal heart rate variability (HRV) is examined under the autonomic nervous system perturbation induced by the head-up-tilt body maneuver. We conducted the multifractal factorization analysis to factor out the common multifractal factor in the joint fluctuation of the beat-to-beat heart rate and electroencephalography data. Evidence of a central link in the multifractal HRV was found, where the transition towards increased (decreased) HRV multifractal complexity is associated with a stronger (weaker) multifractal correlation between the central and autonomic nervous systems.

Pilot testing of the effectiveness of nurse-guided, patient-centered heart failure education for older adults.

PubMed

Mathew, Shiny; Thukha, Henry

2017-12-13

Heart failure (HF) is the most common cause of hospitalization and rehospitalization among those 65 years and older. Effective HF self-management is recommended for reducing readmissions. This pilot study, through a one-group, pretest-posttest design, examines the effects of nurse-guided, patient-centered HF education on readmissions among older adults (n = 26) in a post-acute care unit. All selected participants received 3 sessions of tailored patient education. Their knowledge and self-care skills were measured pre- and post-intervention with the Atlanta Heart Failure Knowledge Test (A-HFKT) and the Self-Care of Heart Failure Index (SCHFI). Patients' HF-related knowledge and self-care skills showed statistically significant improvements, and only 1 patient was rehospitalized for any HF-related reason within 30 days post-discharge. These results suggest that HF rehabilitation teams could support better patient outcomes by assigning nursing staff to provide individualized patient education, as this can help ensure that patients understand discharge instructions for effective self-care. Copyright © 2017 Elsevier Inc. All rights reserved.

Aortic valve prosthesis-patient mismatch and exercise capacity in adult patients with congenital heart disease.

PubMed

van Slooten, Ymkje J; van Melle, Joost P; Freling, Hendrik G; Bouma, Berto J; van Dijk, Arie Pj; Jongbloed, Monique Rm; Post, Martijn C; Sieswerda, Gertjan T; Huis In 't Veld, Anna; Ebels, Tjark; Voors, Adriaan A; Pieper, Petronella G

2016-01-01

To report the prevalence of aortic valve prosthesis-patient mismatch (PPM) in an adult population with congenital heart disease (CHD) and its impact on exercise capacity. Adults with congenital heart disease (ACHD) with a history of aortic valve replacement may outgrow their prosthesis later in life. However, the prevalence and clinical consequences of aortic PPM in ACHD are presently unknown. From the national Dutch Congenital Corvitia (CONCOR) registry, we identified 207 ACHD with an aortic valve prosthesis for this cross-sectional cohort study. Severe PPM was defined as an indexed effective orifice area ≤0.65 cm2/m2 and moderate PPM as an indexed orifice area ≤0.85 cm2/m2 measured using echocardiography. Exercise capacity was reported as percentage of predicted exercise capacity (PPEC). Of the 207 patients, 68% was male, 71% had a mechanical prosthesis and mean age at inclusion was 43.9 years ±11.4. The prevalence of PPM was 42%, comprising 23% severe PPM and 19% moderate PPM. Prevalence of PPM was higher in patients with mechanical prostheses (p<0.001). PPM was associated with poorer exercise capacity (mean PPEC 84% vs. 92%; p=0.048, mean difference =-8.3%, p=0.047). Mean follow-up was 2.6±1.1 years during which New York Heart Association (NYHA) class remained stable in most patients. PPM showed no significant effect on death or hospitalisation during follow-up (p=0.218). In this study we report a high prevalence (42%) of PPM in ACHD with an aortic valve prosthesis and an independent association of PPM with diminished exercise capacity. 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/

Time-resolved contrast-enhanced MR angiography of the thorax in adults with congenital heart disease.

PubMed

Mohrs, Oliver K; Petersen, Steffen E; Voigtlaender, Thomas; Peters, Jutta; Nowak, Bernd; Heinemann, Markus K; Kauczor, Hans-Ulrich

2006-10-01

The aim of this study was to evaluate the diagnostic value of time-resolved contrast-enhanced MR angiography in adults with congenital heart disease. Twenty patients with congenital heart disease (mean age, 38 +/- 14 years; range, 16-73 years) underwent contrast-enhanced turbo fast low-angle shot MR angiography. Thirty consecutive coronal 3D slabs with a frame rate of 1-second duration were acquired. The mask defined as the first data set was subtracted from subsequent images. Image quality was evaluated using a 5-point scale (from 1, not assessable, to 5, excellent image quality). Twelve diagnostic parameters yielded 1 point each in case of correct diagnosis (binary analysis into normal or abnormal) and were summarized into three categories: anatomy of the main thoracic vessels (maximum, 5 points), sequential cardiac anatomy (maximum, 5 points), and shunt detection (maximum, 2 points). The results were compared with a combined clinical reference comprising medical or surgical reports and other imaging studies. Diagnostic accuracies were calculated for each of the parameters as well as for the three categories. The mean image quality was 3.7 +/- 1.0. Using a binary approach, 220 (92%) of the 240 single diagnostic parameters could be analyzed. The percentage of maximum diagnostic points, the sensitivity, the specificity, and the positive and the negative predictive values were all 100% for the anatomy of the main thoracic vessels; 97%, 87%, 100%, 100%, and 96% for sequential cardiac anatomy; and 93%, 93%, 92%, 88%, and 96% for shunt detection. Time-resolved contrast-enhanced MR angiography provides, in one breath-hold, anatomic and qualitative functional information in adult patients with congenital heart disease. The high diagnostic accuracy allows the investigator to tailor subsequent specific MR sequences within the same session.

Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

PubMed

Elder, Robert W; George, Roshan P; McCabe, Nancy M; Rodriguez, Fred H; Book, Wendy M; Mahle, William T; Kirk, Allan D

2015-10-01

Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.

The Hippo pathway in heart development, regeneration, and diseases

PubMed Central

Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

2015-01-01

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 due to 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 very 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 (YAP) transcription co-activator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor (GPCR) signaling, and oxidative stress, are known to play critical roles in cardiac physiology. In addition, YAP has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings regarding the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. PMID:25858067

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

PubMed

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

2006-10-01

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

THERP and HEART integrated methodology for human error assessment

NASA Astrophysics Data System (ADS)

Castiglia, Francesco; Giardina, Mariarosa; Tomarchio, Elio

2015-11-01

THERP and HEART integrated methodology is proposed to investigate accident scenarios that involve operator errors during high-dose-rate (HDR) treatments. The new approach has been modified on the basis of fuzzy set concept with the aim of prioritizing an exhaustive list of erroneous tasks that can lead to patient radiological overexposures. The results allow for the identification of human errors that are necessary to achieve a better understanding of health hazards in the radiotherapy treatment process, so that it can be properly monitored and appropriately managed.

Expansion of Multipotent Stem Cells from the Adult Human Brain

PubMed Central

Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

2013-01-01

The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

Reliability and concurrent validity of a peripheral pulse oximeter and health-app system for the quantification of heart rate in healthy adults.

PubMed

Losa-Iglesias, Marta Elena; Becerro-de-Bengoa-Vallejo, Ricardo; Becerro-de-Bengoa-Losa, Klark Ricardo

2016-06-01

There are downloadable applications (Apps) for cell phones that can measure heart rate in a simple and painless manner. The aim of this study was to assess the reliability of this type of App for a Smartphone using an Android system, compared to the radial pulse and a portable pulse oximeter. We performed a pilot observational study of diagnostic accuracy, randomized in 46 healthy volunteers. The patients' demographic data and cardiac pulse were collected. Radial pulse was measured by palpation of the radial artery with three fingers at the wrist over the radius; a low-cost portable, liquid crystal display finger pulse oximeter; and a Heart Rate Plus for Samsung Galaxy Note®. This study demonstrated high reliability and consistency between systems with respect to the heart rate parameter of healthy adults using three systems. For all parameters, ICC was > 0.93, indicating excellent reliability. Moreover, CVME values for all parameters were between 1.66-4.06 %. We found significant correlation coefficients and no systematic differences between radial pulse palpation and pulse oximeter and a high precision. Low-cost pulse oximeter and App systems can serve as valid instruments for the assessment of heart rate in healthy adults. © The Author(s) 2014.

Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS): rationale, design, and methods.

PubMed

Apers, Silke; Kovacs, Adrienne H; Luyckx, Koen; Alday, Luis; Berghammer, Malin; Budts, Werner; Callus, Edward; Caruana, Maryanne; Chidambarathanu, Shanthi; Cook, Stephen C; Dellborg, Mikael; Enomoto, Junko; Eriksen, Katrine; Fernandes, Susan M; Jackson, Jamie L; Johansson, Bengt; Khairy, Paul; Kutty, Shelby; Menahem, Samuel; Rempel, Gwen; Sluman, Maayke A; Soufi, Alexandra; Thomet, Corina; Veldtman, Gruschen; Wang, Jou-Kou; White, Kamila; Moons, Philip

2015-01-20

Data on patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) are inconsistent and vary across the world. Better understanding of PROs and their differences across cultural and geographic barriers can best be accomplished via international studies using uniform research methods. The APPROACH-IS consortium (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study) was created for this purpose and investigates PROs in adults with CHD worldwide. This paper outlines the project rationale, design, and methods. APPROACH-IS is a cross-sectional study. The goal is to recruit 3500-4000 adults with CHD from 15 countries in five major regions of the world (Asia, Australia, Europe, North and South America). Self-report questionnaires are administered to capture information on PRO domains: (i) perceived health status (12-item Short-form Health Survey & EuroQOL-5D); (ii) psychological functioning (Hospital Anxiety and Depression Scale); (iii) health behaviors (Health-Behavior Scale-Congenital Heart Disease); and (iv) quality of life (Linear Analog Scale & Satisfaction With Life Scale). Additionally, potential explanatory variables are assessed: (i) socio-demographic variables; (ii) medical history (chart review); (iii) sense of coherence (Orientation to Life Questionnaire); and (iv) illness perceptions (Brief Illness Perception Questionnaire). Descriptive analyses and multilevel models will examine differences in PROs and investigate potential explanatory variables. APPROACH-IS represents a global effort to increase research understanding and capacity in the field of CHD, and will have major implications for patient care. Results will generate valuable information for developing interventions to optimize patients' health and well-being. ClinicalTrials.gov: NCT02150603. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prevalence and Predictors of Gaps in Care Among Adult Congenital Heart Disease Patients (The Health, Education and Access Research Trial: HEART-ACHD)

PubMed Central

Gurvitz, Michelle; Valente, Anne Marie; Broberg, Craig; Cook, Stephen; Stout, Karen; Kay, Joseph; Ting, Jennifer; Kuehl, Karen; Earing, Michael; Webb, Gary; Houser, Linda; Opotowsky, Alexander; Harmon, Amy; Graham, Dionne; Khairy, Paul; Gianola, Ann; Verstappen, Amy; Landzberg, Michael

2013-01-01

Objective The goal of this project was to quantify the prevalence of gaps in cardiology care, identify predictors of gaps, and assess barriers to care among adult congenital heart disease (ACHD) patients. Background ACHD patients risk interruptions in care that are associated with undesired outcomes. Methods Patients (≥18years) with first presentation to an ACHD clinic completed a survey regarding gaps in, and barriers to, care. Results Among 12 ACHD centers, 922 subjects (54% female) were recruited. A >3 year gap in cardiology care was identified in 42%, with 8% having gaps longer than a decade. Mean age at first gap was 19.9 years. The majority of respondents had more than high school education, and knew their heart condition. Most common reasons for gaps included feeling well, unaware follow-up required, and complete absence from medical care. Disease complexity was predictive of gap in care with 59% of mild, 42% of moderate and 26% of severe disease subjects reporting gaps (p<0.0001). Clinic location significantly predicted gaps (p<0.0001) while gender, race, and education level did not. Common reasons for returning to care were new symptoms, referral from provider, and desire to prevent problems. Conclusions ACHD patients have gaps in cardiology care; the first lapse commonly occurred around 19 years, a time when transition to adult services is contemplated. Gaps were more common among subjects with mild and moderate diagnoses and at particular locations. These results provide a framework for developing strategies to decrease gaps and address barriers to care in the ACHD population. PMID:23542112

Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

PubMed Central

Yang, Jian; Darley, Richard L; Hallett, Maurice; Evans, W Howard

2009-01-01

Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells and in monocytes and granulocytes in bone marrow and spinal cord. Reverse transcriptase-polymerase chain reaction (RT-PCR) detected only low expression of Cx43 and Cx37. Very low level dye coupling was detected by flow cytometry between CD34+ cells and other Cx43 expressing cells, including HL-1 cardiac cells, and was not inhibited by specific gap junction inhibitors. The results indicate that CD34+ cells are unlikely to communicate via gap junctions and the authors conclude that use of CD34+ cells to repair damaged hearts is unlikely to involve gap junctions. The results concur with the hypothesis that bone marrow cells elicit improved cardiac function through release of undefined paracrine mediators. PMID:20298144

Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.

PubMed

Yang, Kai-Chien; Yamada, Kathryn A; Patel, Akshar Y; Topkara, Veli K; George, Isaac; Cheema, Faisal H; Ewald, Gregory A; Mann, Douglas L; Nerbonne, Jeanne M

2014-03-04

Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs. The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

The Development and Acceptability of a Mobile Application for Tracking Symptoms of Heart Failure Among Older Adults.

PubMed

Portz, Jennifer Dickman; Vehovec, Anton; Dolansky, Mary A; Levin, Jennifer B; Bull, Sheana; Boxer, Rebecca

2018-02-01

Heart failure (HF) is common in older adults. With increases in technology use among older adults, mobile applications may provide a solution for older adults to self-manage symptoms of HF. This article discusses the development and acceptability of a HF symptom-tracking mobile application (HF app). The HF app was developed to allow patients to track their symptoms of HF. Thirty (N = 30) older adults completed an acceptability survey after using the mobile app. The survey used Likert items and open-ended feedback questions. Overall, the acceptability feedback from users was positive with participants indicating that the HF app was both easy to use and understand. Participants identified recommendations for improvement including additional symptoms to track and the inclusion of instructions and reminders. HF is common in older adults, and acceptability of mobile apps is of key importance. The HF app is an acceptable tool for older patients with HF to self-manage their symptoms, identify patterns, and changes in symptoms, and ultimately prevent HF readmission.

A fetal human heart cardiac-inducing RNA (CIR) promotes the differentiation of stem cells into cardiomyocytes.

PubMed

Kochegarov, Andrei; Moses-Arms, Ashley; Lemanski, Larry F

2015-08-01

A specific human fetal heart RNA has been discovered, which has the ability to induce myocardial cell formation from mouse embryonic and human-induced pluripotent stem cells in culture. In this study, commercially obtained RNA from human fetal heart was cloned, sequenced, and synthesized using standard laboratory approaches. Molecular analyses of the specific fetal cardiac-inducing RNA (CIR), revealed that it is a fragment of N-sulfoglucosaminesulfohydrolase and the caspase recruitment domain family member 14 precursor. Stem cells transfected with CIRs often form into spindle-shaped cells characteristic of cardiomyocytes,and express the cardiac-specific contractile protein marker, troponin-T, in addition to tropomyosin and α-actinin as detected by immunohistochemical staining. Expression of these contractile proteins showed organization into sarcomeric myofibrils characteristic of striated cardiac muscle cells. Computer analyses of the RNA secondary structures of the active CIR show significant similarities to a RNA from salamander or myofibril-inducing RNA (MIR), which also promotes non-muscle cells to differentiate into cardiac muscle. Thus, these two RNAs, salamander MIR and the newly discovered human-cloned CIR reported here, appear to have evolutionarily conserved secondary structures suggesting that both play major roles in vertebrate heart development and, particularly, in the differentiation of cardiomyocytes from non-muscle cells during development.

Medication self-management skills and cognitive impairment in older adults hospitalized for heart failure: A cross-sectional study.

PubMed

Howell, Erik H; Senapati, Alpana; Hsich, Eileen; Gorodeski, Eiran Z

2017-01-01

Cognitive impairment is highly prevalent among older adults (aged ≥65 years) hospitalized for heart failure and has been associated with poor outcomes. Poor medication self-management skills have been associated with poor outcomes in this population as well. The presence and extent of an association between cognitive impairment and poor medication self-management skills in this population has not been clearly defined. We assessed the cognition of consecutive older adults hospitalized for heart failure, in relation to their medication self-management skills. We conducted a cross-sectional study of older adults (aged ≥65 years) who were hospitalized for heart failure and were being discharged home. Prior to discharge, we assessed cognition using the Mini-Cog. We also tested patients' ability to read a pill bottle label, open a pill bottle safety cap, and allocate mock pills to a pill box. Pill allocation performance was assessed quantitatively (counts of errors of omission and commission) and qualitatively (patterns suggestive of knowledge-based mistakes, rule-based mistakes, or skill-based slips). Of 55 participants, 22% were found to have cognitive impairment. Patients with cognitive impairment tended to be older as compared to those without cognitive impairment (mean age = 81 vs 76 years, p = NS). Patients with cognitive impairment had a higher prevalence of inability to read pill bottle label (prevalence ratio = 5.8, 95% confidence interval = 3.2-10.5, p = 0.001) and inability to open pill bottle safety cap (prevalence ratio = 3.3, 95% confidence interval = 1.3-8.4, p = 0.03). While most patients (65%) had pill-allocation errors regardless of cognition, those patients with cognitive impairment tended to have more errors of omission (mean number of errors = 48 vs 23, p = 0.006), as well as more knowledge-based mistakes (75% vs 40%, p = 0.03). There is an association between cognitive impairment and poor

Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

PubMed Central

Li, Joan; Wang, Jianchun; Russell, Fraser D; Molenaar, Peter

2005-01-01

The calcineurin (CaN) enzyme–transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. Human right ventricular trabeculae from explanted human (14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1 Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 μM, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. ET-1 increased contractile force in all 13 patients (P<0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P>0.1). FK506 had no effect on contractile force (P=0.12). ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P=0.1). There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKCɛ compared to samples incubated without PKCɛ. Endogenous cardiostimulants which activate Gαq-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate. PMID:15821752

Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease.

PubMed

Law, Yuk M; Keller, Bradley B; Feingold, Brian M; Boyle, Gerard J

2005-02-15

The usefulness of B-type natriuretic peptide (BNP) levels to assess ventricular dysfunction in children and the congenital heart disease population remains largely unknown. We retrospectively analyzed 62 patients with or without known heart disease who had plasma BNP measured for the investigation of new or severity grading of known ventricular dysfunction. BNP levels were significantly higher in patients with ventricular dysfunction (mean 623 +/- 146 pg/ml, range 5 to 5,000) than in patients without ventricular dysfunction (mean 22 +/- 5 pg/ml, range 5 to 63; p <0.01). Using a cutoff of 40 pg/ml, BNP levels detected heart disease associated with ventricular dysfunction at a sensitivity of 85%, specificity of 81%, positive predictive value of 92%, and negative predictive value of 68%. The degree of BNP elevation was also associated with the severity of heart failure and high ventricular filling pressures. Plasma BNP elevation can be a reliable test in children and young adults with various kinds of congenital heart disease resulting in ventricular dysfunction.

The effect of nurse-led education on hospitalisation, readmission, quality of life and cost in adults with heart failure. A systematic review.

PubMed

Rice, Helena; Say, Richard; Betihavas, Vasiliki

2018-03-01

The purpose of this systematic review was to highlight the effect of nurse-led 1:1 patient education sessions on Quality of Life (QoL), readmission rates and healthcare costs for adults with heart failure (HF) living independently in the community. A systematic review of randomised control trials was undertaken. Using the search terms nurse, education, heart failure, hospitalisation, readmission, rehospitalisation, economic burden, cost, expenditure and quality of life in PubMed, CINAHL and Google Scholar databases were searched. Papers pertaining to nurse-led 1:1 HF disease management of education of adults in the community with a history of HF were reviewed. The results of this review identified nurse-led education sessions for adults with HF contribute to reduction in hospital readmissions, reduction in hospitalisation and a cost benefit. Additionally, higher functioning and improved QoL were also identified. These results suggest that nurse-led patient education for adults with HF improves QoL and reduces hospital admissions and readmissions. Nurse-led education can be delivered utilising diverse methods and impact to reduce readmission as well as hospitalisation. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Developing a novel comprehensive framework for the investigation of cellular and whole heart electrophysiology in the in situ human heart: historical perspectives, current progress and future prospects.

PubMed

Taggart, Peter; Orini, Michele; Hanson, Ben; Hayward, Martin; Clayton, Richard; Dobrzynski, Halina; Yanni, Joseph; Boyett, Mark; Lambiase, Pier D

2014-08-01

Understanding the mechanisms of fatal ventricular arrhythmias is of great importance. In view of the many electrophysiological differences that exist between animal species and humans, the acquisition of basic electrophysiological data in the intact human heart is essential to drive and complement experimental work in animal and in-silico models. Over the years techniques have been developed to obtain basic electrophysiological signals directly from the patients by incorporating these measurements into routine clinical procedures which access the heart such as cardiac catheterisation and cardiac surgery. Early recordings with monophasic action potentials provided valuable information including normal values for the in vivo human heart, cycle length dependent properties, the effect of ischaemia, autonomic nervous system activity, and mechano-electric interaction. Transmural recordings addressed the controversial issue of the mid myocardial "M" cell. More recently, the technique of multielectrode mapping (256 electrodes) developed in animal models has been extended to humans, enabling mapping of activation and repolarisation on the entire left and right ventricular epicardium in patients during cardiac surgery. Studies have examined the issue of whether ventricular fibrillation was driven by a "mother" rotor with inhomogeneous and fragmented conduction as in some animal models, or by multiple wavelets as in other animal studies; results showed that both mechanisms are operative in humans. The simpler spatial organisation of human VF has important implications for treatment and prevention. To link in-vivo human electrophysiological mapping with cellular biophysics, multielectrode mapping is now being combined with myocardial biopsies. This technique enables region-specific electrophysiology changes to be related to underlying cellular biology, for example: APD alternans, which is a precursor of VF and sudden death. The mechanism is incompletely understood but related

Human Catestatin Peptides Differentially Regulate Infarct Size in the Ischemic-Reperfused Rat Heart

PubMed Central

Brar, Bhawanjit K.; Helgeland, Erik; Mahata, Sushil K.; Zhang, Kuixing; O'Connor, Daniel T.; Helle, Karen B.; Jonassen, Anne K.

2010-01-01

In acute myocardial infarction increased plasma levels of chromogranin A is correlated with decreased survival. At the human chromogranin A gene locus there are two naturally occurring amino acid substitution variants within the catestatin region, i.e. Gly364 Ser and Pro370Leu, displaying differential potencies towards inhibition of nicotinic cholinergic agonist-evoked catecholamine secretion from sympathochromaffin cells and different degrees of processing from the prohormone. Here, we examine whether two of the variants and the wild type catestatin may affect the development of infarct size during ischemic reperfusion in the Langendorff rat heart model. The hearts were subjected to regional ischemia followed by reperfusion in the presence or absence of synthetic variants of human catestatin. Compared to the Gly364Ser variant both the wild type and the Pro370Leu variant increased infarct size while decreasing the cardiac levels of phosphorylated Akt and two of its downstream targets, FoxO1 and BAD. In conclusion, these findings suggest that, in contrast to the Gly364Ser variant, the wild type catestatin and the Pro370Leu variant (allele frequency ~0.3%) increased myocardial infarct size via a mechanism involving dephosphorylation of Akt and the two downstream targets during ischemic reperfusion in the isolated rat heart. PMID:20655339

Transition from paediatric to adult care of adolescent patients with congenital heart disease: a pathway to optimal care.

PubMed

Strijbosch, A M M; Zwart, R; Blom, N A; Bouma, B J; Groenink, M; Boekholdt, S M; de Winter, R; Mulder, B J M; Backx, A P

2016-11-01

Adolescents with congenital heart disease transition from a paediatric to an adult setting. This is associated with loss-to-follow-up and suboptimal care. Increasing numbers of patients justify a special program. In this study we evaluated the cooperative program between paediatric and adult cardiology departments in a tertiary referral centre. In this retrospective study, patients with congenital heart disease with at least one appointment scheduled at the transition program between January 2010 and January 2015 were included. They were seen by a paediatric cardiologist at the age of 15 years in the paediatric department and from age 18 to 25 in the adult department. Demographic and medical data were collected from the electronic patient files. A total of 193 patients (105 males, 88 females) were identified. Sex distribution was almost equal. Most patients were 18-21 years of age. The largest group, 128 patients (67 %), lived within 50 kilometres of our hospital. Paediatric cardiologists referred 157 (81 %) of patients. General practitioners and cardiologists from outside our centre were important referrers for patients lost to follow-up, together accounting for 9 %. A total of 34 (18 %) patients missed an appointment without notification. Repeat offenders, 16 of 34 patients, formed a significant minority within this group. A total of 114 (59 %) patients were attending school, 46 (24 %) were employed, and 33 (17 %) patients were inactive. Activities are in line with capabilities. A nurse practitioner was involved with the 7 % with complex and psychosocial problems. Moderately severe congenital heart defects formed the largest patient category of 102 (53 %) patients. In 3 % of patients the diagnosis had to be revised or was significantly incomplete. In 30 (16 %) patients, cardiac diagnosis was part of a syndrome. Of the 193 patients, 117 (92 %) were in NYHA class I, with 12 (6 %) and 4 (2 %) patients falling into classes

Impact of space weather on human heart rate during the years 2011-2013

NASA Astrophysics Data System (ADS)

Galata, E.; Ioannidou, S.; Papailiou, M.; Mavromichalaki, H.; Paravolidakis, K.; Kouremeti, M.; Rentifis, L.; Simantirakis, E.; Trachanas, K.

2017-08-01

During the last years a possible link between different levels of solar and geomagnetic disturbances and human physiological parameters is suggested by several published studies. In this work the examination of the potential association between heart rate variations and specific space weather activities was performed. A total of 482 individuals treated at Hippocratio General Hospital in Athens, the Cardiology clinics of Nikaia General Hospital in Piraeus and the Heraklion University Hospital in Crete, Greece, were assessed from July 2011 to April 2013. The heart rate of the individuals was recorded by a Holter monitor on a n hourly basis, while the hourly variations of the cosmic ray intensity measured by the Neutron Monitor Station of the Athens University and of the geomagnetic index Dst provided by the Kyoto Observatory were used. The ANalysis Of VAriance (ANOVA) and the Multiple Linear Regression analysis were used for analysis of these data. A statistically significant effect of both cosmic rays and geomagnetic activity on heart rate was observed, which may indicate that changes in space weather could be linked to heart rate variations.

Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle.

PubMed

Copeland, O'Neal; Sadayappan, Sakthivel; Messer, Andrew E; Steinen, Ger J M; van der Velden, Jolanda; Marston, Steven B

2010-12-01

A unique feature of MyBP-C in cardiac muscle is that it has multiple phosphorylation sites. MyBP-C phosphorylation, predominantly by PKA, plays an essential role in modulating contractility as part of the cellular response to β-adrenergic stimulation. In vitro studies indicate MyBP-C can be phosphorylated at Serine 273, 282, 302 and 307 (mouse sequence) but little is known about the level of MyBP-C phosphorylation or the sites phosphorylated in heart muscle. Since current methodologies are limited in specificity and are not quantitative we have investigated the use of phosphate affinity SDS-PAGE together with a total anti MyBP-C antibody and a range of phosphorylation site-specific antibodies for the main sites (Ser-273, -282 and -302). With these newly developed methods we have been able to make a detailed quantitative analysis of MyBP-C phosphorylation in heart tissue in situ. We have found that MyBP-C is highly phosphorylated in non-failing human (donor) heart or mouse heart; tris and tetra-phosphorylated species predominate and less than 10% of MyBP-C is unphosphorylated (0, 9.3 ± 1%: 1P, 13.4 ± 2.7%: 2P, 10.5 ± 3.3%: 3P, 28.7 ± 3.7%: 4P, 36.4 ± 2.7%, n=21). Total phosphorylation was 2.7 ± 0.07 mol Pi/mol MyBP-C. In contrast in failing heart and in myectomy samples from HCM patients the majority of MyBP-C was unphosphorylated. Total phosphorylation levels were 23% of normal in failing heart myofibrils (0, 60.1 ± 2.8%: 1P, 27.8 ± 2.8%: 2P, 4.8 ± 2.0%: 3P, 3.7 ± 1.2%: 4P, 2.8 ± 1.3%, n=19) and 39% of normal in myectomy samples. The site-specific antibodies showed a distinctive distribution pattern of phosphorylation sites in the multiple phosphorylation level species. We found that phosphorylated Ser-273, Ser-282 and Ser-302 were all present in the 4P band of MyBP-C but none of them were significant in the 1P band, indicating that there must be at least one other site of MyBP-C phosphorylation in human heart. The pattern of phosphorylation at the

In vitro sensitivity of cholinesterases and [3H]oxotremorine-M binding in heart and brain of adult and aging rats to organophosphorus anticholinesterases.

PubMed

Mirajkar, Nikita; Pope, Carey N

2008-10-15

Organophosphorus (OP) insecticides elicit toxicity via acetylcholinesterase inhibition, allowing acetylcholine accumulation and excessive stimulation of cholinergic receptors. Some OP insecticides bind to additional macromolecules including butyrylcholinesterase and cholinergic receptors. While neurotoxicity from OP anticholinesterases has been extensively studied, effects on cardiac function have received less attention. We compared the in vitro sensitivity of acetylcholinesterase, butyrylcholinesterase and [(3)H]oxotremorine-M binding to muscarinic receptors in the cortex and heart of adult (3 months) and aging (18 months) rats to chlorpyrifos, methyl parathion and their active metabolites chlorpyrifos oxon and methyl paraoxon. Using selective inhibitors, the great majority of cholinesterase in brain was defined as acetylcholinesterase, while butyrylcholinesterase was the major cholinesterase in heart, regardless of age. In the heart, butyrylcholinesterase was markedly more sensitive than acetylcholinesterase to inhibition by chlorpyrifos oxon, and butyrylcholinesterase in tissues from aging rats was more sensitive than enzyme from adults, possibly due to differences in A-esterase mediated detoxification. Relatively similar differences were noted in brain. In contrast, acetylcholinesterase was more sensitive than butyrylcholinesterase to methyl paraoxon in both heart and brain, but no age-related differences were noted. Both oxons displaced [(3)H]oxotremorine-M binding in heart and brain of both age groups in a concentration-dependent manner. Chlorpyrifos had no effect but methyl parathion was a potent displacer of binding in heart and brain of both age groups. Such OP and age-related differences in interactions with cholinergic macromolecules may be important because of potential for environmental exposures to insecticides as well as the use of anticholinesterases in age-related neurological disorders.

IN VITRO SENSITIVITY OF CHOLINESTERASES AND [3H]OXOTREMORINE-M BINDING IN HEART AND BRAIN OF ADULT AND AGING RATS TO ORGANOPHOSPHORUS ANTICHOLINESTERASES

PubMed Central

Mirajkar, Nikita; Pope, Carey N.

2008-01-01

Organophosphorus (OP) insecticides elicit toxicity via acetylcholinesterase inhibition, allowing acetylcholine accumulation and excessive stimulation of cholinergic receptors. Some OP insecticides bind to additional macromolecules including butyrylcholinesterase and cholinergic receptors. While neurotoxicity from OP anticholinesterases has been extensively studied, effects on cardiac function have received less attention. We compared the in vitro sensitivity of acetylcholinesterase, butyrylcholinesterase and [3H]oxotremorine-M binding to muscarinic receptors in the cortex and heart of adult (3 months) and aging (18 months) rats to chlorpyrifos, methyl parathion and their active metabolites chlorpyrifos oxon and methyl paraoxon. Using selective inhibitors, the great majority of cholinesterase in brain was defined as acetylcholinesterase, while butyrylcholinesterase was the major cholinesterase in heart, regardless of age. In the heart, butyrylcholinesterase was markedly more sensitive than acetylcholinesterase to inhibition by chlorpyrifos oxon, and butyrylcholinesterase in tissues from aging rats was more sensitive than enzyme from adults, possibly due to differences in A-esterase mediated detoxification. Relatively similar differences were noted in brain. In contrast, acetylcholinesterase was more sensitive than butyrylcholinesterase to methyl paraoxon in both heart and brain, but no age-related differences were noted. Both oxons displaced [3H]oxotremorine-M binding in heart and brain of both age groups in a concentration-dependent manner. Chlorpyrifos had no effect but methyl parathion was a potent displacer of binding in heart and brain of both age groups. Such OP and age-related differences in interactions with cholinergic macromolecules may be important because of potential for environmental exposures to insecticides as well as the use of anticholinesterases in age-related neurological disorders. PMID:18761328

Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults.

PubMed

Kortchinsky, Talna; Mussot, Sacha; Rezaiguia, Saïda; Artiguenave, Margaux; Fadel, Elie; Stephan, François

2016-09-01

After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1-year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Profiling and Validation of the Circular RNA Repertoire in Adult Murine Hearts.

PubMed

Jakobi, Tobias; Czaja-Hasse, Lisa F; Reinhardt, Richard; Dieterich, Christoph

2016-08-01

For several decades, cardiovascular disease has been the leading cause of death throughout all countries. There is a strong genetic component to many disease subtypes (e.g., cardiomyopathy) and we are just beginning to understand the relevant genetic factors. Several studies have related RNA splicing to cardiovascular disease and circular RNAs (circRNAs) are an emerging player. circRNAs, which originate through back-splicing events from primary transcripts, are resistant to exonucleases and typically not polyadenylated. Initial functional studies show clear phenotypic outcomes for selected circRNAs. We provide, for the first time, a comprehensive catalogue of RNase R-resistant circRNA species for the adult murine heart. This work combines state-of-the-art circle sequencing with our novel DCC software to explore the circRNA landscape of heart tissue. Overall, we identified 575 circRNA species that pass a beta-binomial test for enrichment (false discovery rate of 1%) in the exonuclease-treated sequencing sample. Several circRNAs can be directly attributed to host genes that have been previously described as associated with cardiovascular disease. Further studies of these candidate circRNAs may reveal disease-relevant properties or functions of specific circRNAs. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Comparison at Necropsy of Heart Weight in Women Aged 20 to 29 Years With Fatal Trauma or Chemical Intoxication Versus Fatal Natural Cause (A Search for the Normal Adult Heart Weight).

PubMed

Blackbourne, Brian D; Vasudevan, Anupama; Roberts, William C

2017-03-01

The present obesity epidemic makes determining the normal heart weight in adults difficult. This study examines the heart weight at autopsy in 104 women aged 20 to 29 years who died in 1978 to 1980 before the overweight epidemic ensued. Of the 104 cases, the hearts weighed ≤300 g in 86 (83%) and >300 g in 18 (17%). Of the 67 cases dying from an unnatural cause (trauma or chemical intoxication), only 3 (4%) had hearts weighing >300 g; of the 37 patients dying from a variety of natural causes, 15 (41%) had hearts weighing >300 g (p <0.001). The body mass index (BMI) was ≤25 kg/m 2 in 82 cases (79%) and the hearts in them ranged from 120 to 400 g (mean 262 ± 51; median 257 g); of the 22 cases (21%) in whom the BMI was >25 kg/m 2 , the hearts ranged from 230 to 850 g (mean 351 ± 142; median 300 g). In conclusion, the cases dying from an unnatural cause had smaller mean heart weights than those women dying from a natural cause and those with a normal BMI (≤25 kg/m 2 ) had smaller mean heart weights than those with a BMI >25 kg/m 2 . The normal heart weight in young women dying from an unnatural cause with few exceptions is <300 g. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiopulmonary Exercise Testing in Adult Congenital Heart Disease.

PubMed

Mantegazza, Valentina; Apostolo, Anna; Hager, Alfred

2017-07-01

Recently, the number of patients with congenital heart diseases reaching adulthood has been progressively increasing in developed countries, and new issues are emerging: the evaluation of their capacity to cope with physical activity and whether this knowledge can be used to optimize medical management. A symptom-limited cardiopulmonary exercise test has proven to be an essential tool, because it can objectively evaluate the functional cardiovascular capacity of these patients, identify the pathological mechanisms of the defect (circulatory failure, shunts, and/or pulmonary hypertension), and help prescribe an individualized rehabilitation program when needed. The common findings on cardiopulmonary exercise testing in patients with congenital heart diseases are a reduced peak [Formula: see text]o 2 , an early anaerobic threshold, a blunted heart rate response, a reduced increase of Vt, and an increased [Formula: see text]e/[Formula: see text]co 2 . All these measures suggest common pathophysiological abnormalities: (1) a compromised exercise capacity from anomalies affecting the heart, vessels, lungs, or muscles; (2) chronotropic incompetence secondary to cardiac autonomic dysfunction or β-blockers and antiarrhythmic therapy; and (3) ventilatory inefficiency caused by left-heart failure with pulmonary congestion, pulmonary hypertension, pulmonary obstructive vascular disease, or cachexia. Most of these variables also have prognostic significance. For these patients, cardiopulmonary exercise testing allows evaluation and decisions affecting lifestyle and therapeutic interventions.

Pharmacological and physiological assessment of serotonin formation and degradation in isolated preparations from mouse and human hearts.

PubMed

Gergs, Ulrich; Jung, Franziska; Buchwalow, Igor B; Hofmann, Britt; Simm, Andreas; Treede, Hendrik; Neumann, Joachim

2017-12-01

Using transgenic (TG) mice that overexpress the human serotonin (5-HT) 4a receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor 5-hydroxy-tryptophan (5-HTP) can exert inotropic and chronotropic effects in cardiac preparations from TG mice but not from wild-type (WT) mice; similar results were found in human atrial preparations as well as in intact TG animals using echocardiography. Moreover, by immunohistochemistry we could detect 5-HT metabolizing enzymes and 5-HT transporters in mouse hearts as well as in human atria. Hence, in the presence of an inhibitor of aromatic l-amino acid decarboxylase, the positive inotropic effects of 5-HTP were absent in TG and isolated human atrial preparations, and, moreover, inhibitors of enzymes involved in 5-HT degradation enhanced the efficacy of 5-HT in TG atria. A releaser of neurotransmitters increased inotropy in the isolated TG atrium, and this effect could be blocked by a 5-HT 4a receptor antagonist. Fluoxetine, an inhibitor of 5-HT uptake, elevated the potency of 5-HT to increase contractility in the TG atrium. In addition, inhibitors of organic cation and monoamine transporters apparently reduced the positive inotropic potency of 5-HT in the TG atrium. Hence, we tentatively conclude that a local production and degradation of 5-HT in the mammalian heart and more specifically in mammalian myocytes probably occurs. Conceivably, this formation of 5-HT and possibly impaired degradation may be clinically relevant in cases of unexplained tachycardia and other arrhythmias. NEW & NOTEWORTHY The present work suggests that inotropically active serotonin (5-HT) can be formed in the mouse and human heart and probably by cardiomyocytes themselves. Moreover, active degradation of 5-HT seems to occur in the mammalian heart. These findings may again

Heart rate variability of human in hypoxic oxygen-argon environment

NASA Astrophysics Data System (ADS)

Khayrullina, Rezeda; Smoleevskiy, Alexandr; Bubeev, Yuri

Human adaptive capacity, reliability and stability in extreme environments depend primarily on the individual resistance to stresses, includes both innate and acquired components. We have conducted studies in six healthy subjects - men aged between 24 to 42 years who psychophysiological indicators acterizing the severity of stress reactions studied directly during an emergency situation, before and after it. The subjects were in a hypoxic oxygen-argon atmosphere 10 days. Cardiovascular system is one of the first to respond to stressful reaction. The method of heart rate variability (HRV) allows us to estimate balance of sympathetic and parasympathetic parts of vegetative nervous system. In the course of the baseline study it was found that resting heart rate (HR) in the examined individuals is within normal limits. During the experiment in all subjects there was a trend towards more frequent heartbeat. Each subject at one stage or another stay in a hypoxic oxygen-argon environment heart rate go beyond the group norm, but the extent and duration of these abnormalities were significantly different. Marked increase in middle heart rate during of subjects experiment, fluctuating within a wide range (from 2.3% to 29.1%). Marked increase in middle heart rate during of subjects experiment, fluctuating within a wide range (from 2.3% to 29.1%). This suggests that the ability to adapt to living in the investigated gas environment have marked individual differences. SDNN (mean square deviation of all R-R intervals) is the integral indicator of the total effect of the sinus node to the sympathetic and parasympathetic parts of vegetative nervous system, as well as indicating the higher functional reserves of the cardiovascular systems. Increase in heart rate in the majority of subject was accompanied by an increase in individual SDNN. This suggests that the parasympathetic system is able to balance the increase in activity of the sympathetic system, and functional reserves are

Effect of Environmental Chemical Exposures on Adult Human Cardiac Progenitor Cell Viability and Differentiation

EPA Science Inventory

Cell biology has revealed that the adult heart is not a terminally differentiated organ but is capable of generating new cardiomyocytes (CMs) from cardiac stem cells (CSC) and/or progenitor cells (CPC) throughout life. The impact that environmental chemical exposures have on adul...

Facilitators of and Barriers to mHealth Adoption in Older Adults With Heart Failure.

PubMed

Cajita, Maan Isabella; Hodgson, Nancy A; Lam, Katherine Wai; Yoo, Sera; Han, Hae-Ra

2018-05-04

The purpose of this descriptive, exploratory study was to assess the perceptions of older adults with heart failure regarding the use of mobile technology and to identify potential facilitators of and barriers to mHealth adoption. Semistructured interviews were used to collect data. Transcripts were analyzed using qualitative content analysis. The findings indicated that older adults do not base their intention to use mHealth solely on perceived ease of use and perceived usefulness, as outlined in the Technology Acceptance Model. The following themes emerged from the content analysis: facilitators included previous experience with mobile technology, willingness to learn mHealth, ease of use, presence of useful features, adequate training, free equipment, and doctor's recommendation; barriers included lack of knowledge regarding how to use mHealth, decreased sensory perception, lack of need for technology, poorly designed interface, cost of technology, and limited/fixed income. Overall, the findings suggest that older adults are willing to use mobile health technology, albeit with reservations. Future researchers who seek to implement mHealth-based interventions should address person-related, technology-related, and contextual barriers, and simultaneously capitalize on the influence of potential facilitators, such as a physician's recommendation, to promote mHealth adoption.

Epigenomic Landscape of Human Fetal Brain, Heart, and Liver.

PubMed

Yan, Liying; Guo, Hongshan; Hu, Boqiang; Li, Rong; Yong, Jun; Zhao, Yangyu; Zhi, Xu; Fan, Xiaoying; Guo, Fan; Wang, Xiaoye; Wang, Wei; Wei, Yuan; Wang, Yan; Wen, Lu; Qiao, Jie; Tang, Fuchou

2016-02-26

The epigenetic regulation of spatiotemporal gene expression is crucial for human development. Here, we present whole-genome chromatin immunoprecipitation followed by high throughput DNA sequencing (ChIP-seq) analyses of a wide variety of histone markers in the brain, heart, and liver of early human embryos shortly after their formation. We identified 40,181 active enhancers, with a large portion showing tissue-specific and developmental stage-specific patterns, pointing to their roles in controlling the ordered spatiotemporal expression of the developmental genes in early human embryos. Moreover, using sequential ChIP-seq, we showed that all three organs have hundreds to thousands of bivalent domains that are marked by both H3K4me3 and H3K27me3, probably to keep the progenitor cells in these organs ready for immediate differentiation into diverse cell types during subsequent developmental processes. Our work illustrates the potentially critical roles of tissue-specific and developmental stage-specific epigenomes in regulating the spatiotemporal expression of developmental genes during early human embryonic development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Zoonotic bacterial meningitis in human adults.

PubMed

van Samkar, Anusha; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2016-09-13

To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults. We identified 16 zoonotic bacteria causing meningitis in adults. Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by human pathogens, and the incidence has a strong regional distribution. Zoonotic bacterial meningitis is mainly associated with animal contact, consumption of animal products, and an immunocompromised state of the patient. In a high proportion of zoonotic bacterial meningitis cases, CSF analysis showed only a mildly elevated leukocyte count. The recommended antibiotic therapy differs per pathogen, and the overall mortality is low. Zoonotic bacterial meningitis is uncommon but is associated with specific complications. The suspicion should be raised in patients with bacterial meningitis who have recreational or professional contact with animals and in patients living in regions endemic for specific zoonotic pathogens. An immunocompromised state is associated with a worse prognosis. Identification of risk factors and underlying disease is necessary to improve treatment. © 2016 American Academy of Neurology.

Outcomes of a Telehealth Intervention for Homebound Older Adults with Heart or Chronic Respiratory Failure: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Gellis, Zvi D.; Kenaley, Bonnie; McGinty, Jean; Bardelli, Ellen; Davitt, Joan; Ten Have, Thomas

2012-01-01

Purpose: Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. Design and Methods: We report on a randomized controlled trial examining the impact of a multifaceted…

Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines

PubMed Central

Bäcker, Henrik; Polgár, Livia; Soós, Pal; Lajkó, Eszter; Láng, Orsolya; Merkely, Bela; Szabó, Gabor; Dohmen, Pascal M.; Weymann, Alexander; Kőhidai, Laszlo

2017-01-01

Background Experiments on porcine heart scaffold represent significant assays in development of immunoneutral materials for cardiac surgery. Characterization of cell-cell and cell-scaffold interactions is essential to understand the homing process of cardiac cells into the scaffolds. Material/Methods In the present study, the highly sensitive and real-time impedimetric technique of xCELLigence SP was used to monitor cell adhesion, which is the key process of recellularization in heart scaffolds. Our objectives were: (i) to characterize the effect of decellularized porcine heart scaffold on cell adhesion of human cardiovascular cells potentially used in the recellularization process; and (ii) to investigate cell-extracellular matrix element interactions for building artificial multi-layer systems, applied as cellular models of recellularization experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were investigated and the effect of decellularized porcine heart scaffold (HS) and fibronectin on cell adhesion was examined. Adhesion was quantified as slope of curves. Results Heart scaffold had neutral effect on cardiomyocytes as well as on endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin (1.480±0.021) compared to control (0.745±0.029). The combination of fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407±0.634) than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly strong adhesion profiles with marked enhancer effect by fibronectin. Conclusions Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells at the cell biological level, while fibronectin has strong cell adhesion-inducer effect, as well as an enhancer effect on activity of HS. Consequently, decellularized porcine hearts could be used as scaffolds for recellularization with cardiomyocytes and endothelial cells with fibronectin acting as a regulator, leading to construction of working bioartificial

Prevalence of Rheumatic Heart Disease in Children and Young Adults in Nicaragua

PubMed Central

Paar, John A.; Berrios, Nubia M.; Rose, John D.; Cáceres, Mercedes; Peña, Rodolfo; Pérez, Wilton; Chen-Mok, Mario; Jolles, Erik; Dale, James B.

2010-01-01

Rheumatic heart disease (RHD) results in morbidity and mortality that is disproportionate among people in developing countries compared to those living in economically developed countries. The global burden of disease is uncertain because most previous studies to determine the prevalence of RHD in children relied on clinical screening criteria that lacked the sensitivity to detect most cases. The present study was performed to determine the prevalence of RHD in children and young adults in León, Nicaragua, an area previously thought to have a high prevalence of RHD. This was an observational study of 3150 children, ages 5–15, and 489 adults, ages 20–35, randomly selected from urban and rural areas of León. Cardiopulmonary exams and echo-Doppler studies were performed on all subjects. Echo-Doppler diagnosis of RHD was based on pre-defined consensus criteria that were developed by a WHO/NIH working group. The overall prevalence of RHD in children was 48/1000 (95% C.I. = 35/1000–60/1000. The prevalence in urban children was 34/1000 and in rural children it was 80/1000. Using more stringent echo-Doppler criteria designed to diagnose definite RHD in adults, the prevalence was 22/1000 (95% C.I.=8/1000–37/1000). In conclusion, the prevalence of RHD among children and adults in this economically disadvantaged population far exceeds previously predicted rates. The findings underscore the potential health and economic burden of acute rheumatic fever and RHD and support the need for more effective measures of prevention, which may include safe, effective and affordable vaccines to prevent the streptococcal infections that trigger the disease. PMID:20538135

Exaggerated heart rate oscillations during two meditation techniques.

PubMed

Peng, C K; Mietus, J E; Liu, Y; Khalsa, G; Douglas, P S; Benson, H; Goldberger, A L

1999-07-31

We report extremely prominent heart rate oscillations associated with slow breathing during specific traditional forms of Chinese Chi and Kundalini Yoga meditation techniques in healthy young adults. We applied both spectral analysis and a novel analytic technique based on the Hilbert transform to quantify these heart rate dynamics. The amplitude of these oscillations during meditation was significantly greater than in the pre-meditation control state and also in three non-meditation control groups: i) elite athletes during sleep, ii) healthy young adults during metronomic breathing, and iii) healthy young adults during spontaneous nocturnal breathing. This finding, along with the marked variability of the beat-to-beat heart rate dynamics during such profound meditative states, challenges the notion of meditation as only an autonomically quiescent state.

The effect of garden designs on mood and heart output in older adults residing in an assisted living facility.

PubMed

Goto, Seiko; Park, Bum-Jin; Tsunetsugu, Yuko; Herrup, Karl; Miyazaki, Yoshifumi

2013-01-01

The objective of this study is to trace short-term changes in mood and heart function in elderly individuals in response to exposure to different landscaped spaces. Nineteen elderly but cognitively intact residents of an assisted living facility participated in the study. They were exposed to three landscaped spaces: a Japanese style garden, an herb garden, and a simple landscaped area planted with a single tree. To assess the effect of different landscaped spaces on older adults, individuals were monitored for mood and cardiac function in response to short exposures to spaces. Mood state was assessed using Profile of Mood States (POMS) before and after viewing the spaces. Cardiac output was assessed using a portable electrocardiograph monitor before and during the viewing. We found that the structured gardens evoked greater responses in all outcome measures. Scores on the POMS improved after observation of the two organized gardens compared to responses to the simple landscaped space with a single tree. During the observation period, heart rate was significantly lower in the Japanese garden than in the other environments, and sympathetic function was significantly lower as well. We conclude that exposure to organized gardens can affect both the mood and cardiac physiology of elderly individuals. Our data further suggest that these effects can differ depending on the types of landscape to which an individual is exposed. Elderly, Japanese garden, herb garden, heart rate, mood, healing environmentPreferred Citation: Goto, S., Park, B-J., Tsunetsugu, Y., Herrup, K., & Miyazaki, Y. (2013). The effect of garden designs on mood and heart output in older adults residing in an assisted living facility. Health Environments Research & Design Journal 6(2), pp 27-42.

Heart Rate and Heart Rate Variability in Dairy Cows with Different Temperament and Behavioural Reactivity to Humans

PubMed Central

Tőzsér, János; Szenci, Ottó; Póti, Péter; Pajor, Ferenc

2015-01-01

From the 1990s, extensive research was started on the physiological aspects of individual traits in animals. Previous research has established two extreme (proactive and reactive) coping styles in several animal species, but the means of reactivity with the autonomic nervous system (ANS) activity has not yet been investigated in cattle. The aim of this study was the characterization of cardiac autonomic activity under different conditions in cows with different individual characteristics. For this purpose, we investigated heart rate and ANS-related heart rate variability (HRV) parameters of dairy cows (N = 282) on smaller- and larger-scale farms grouped by (1) temperament and (2) behavioural reactivity to humans (BRH). Animals with high BRH scores were defined as impulsive, while animals with low BRH scores were defined as reserved. Cardiac parameters were calculated for undisturbed lying (baseline) and for milking bouts, the latter with the presence of an unfamiliar person (stressful situation). Sympathetic tone was higher, while vagal activity was lower in temperamental cows than in calm animals during rest both on smaller- and larger-scale farms. During milking, HRV parameters were indicative of a higher sympathetic and a lower vagal activity of temperamental cows as compared to calm ones in farms of both sizes. Basal heart rate did not differ between BRH groups either on smaller- or larger-scale farms. Differences between basal ANS activity of impulsive and reserved cows reflected a higher resting vagal and lower sympathetic activity of reserved animals compared to impulsive ones both on smaller- and larger-scale farms. There was no difference either in heart rate or in HRV parameters between groups during milking neither in smaller- nor in larger-scale farms. These two groupings allowed to draw possible parallels between personality and cardiac autonomic activity during both rest and milking in dairy cows. Heart rate and HRV seem to be useful for

Effects of Age and Heart Failure on Human Cardiac Stem Cell Function

PubMed Central

Cesselli, Daniela; Beltrami, Antonio P.; D'Aurizio, Federica; Marcon, Patrizia; Bergamin, Natascha; Toffoletto, Barbara; Pandolfi, Maura; Puppato, Elisa; Marino, Laura; Signore, Sergio; Livi, Ugolino; Verardo, Roberto; Piazza, Silvano; Marchionni, Luigi; Fiorini, Claudia; Schneider, Claudio; Hosoda, Toru; Rota, Marcello; Kajstura, Jan; Anversa, Piero; Beltrami, Carlo A.; Leri, Annarosa

2011-01-01

Currently, it is unknown whether defects in stem cell growth and differentiation contribute to myocardial aging and chronic heart failure (CHF), and whether a compartment of functional human cardiac stem cells (hCSCs) persists in the decompensated heart. To determine whether aging and CHF are critical determinants of the loss in growth reserve of the heart, the properties of hCSCs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent hCSCs. Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21Cip1 and p16INK4a expression. CHF had similar consequences for hCSCs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent hCSCs may condition the evolution of the decompensated myopathy. A correlation was found previously between telomere length in circulating bone marrow cells and cardiovascular diseases, but that analysis was restricted to average telomere length in a cell population, neglecting the fact that telomere attrition does not occur uniformly in all cells. The present study provides the first demonstration that dysfunctional telomeres in hCSCs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of hCSCs and to sort young cells with potential therapeutic efficacy. PMID:21703415

Haploinsufficiency of TAB2 Causes Congenital Heart Defects in Humans

PubMed Central

Thienpont, Bernard; Zhang, Litu; Postma, Alex V.; Breckpot, Jeroen; Tranchevent, Léon-Charles; Van Loo, Peter; Møllgård, Kjeld; Tommerup, Niels; Bache, Iben; Tümer, Zeynep; van Engelen, Klaartje; Menten, Björn; Mortier, Geert; Waggoner, Darrel; Gewillig, Marc; Moreau, Yves; Devriendt, Koen; Larsen, Lars Allan

2010-01-01

Congenital heart defects (CHDs) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their etiology remains often obscure. We identified a locus for CHDs on 6q24-q25. Genotype-phenotype correlations in 12 patients carrying a chromosomal deletion on 6q delineated a critical 850 kb region on 6q25.1 harboring five genes. Bioinformatics prioritization of candidate genes in this locus for a role in CHDs identified the TGF-β-activated kinase 1/MAP3K7 binding protein 2 gene (TAB2) as the top-ranking candidate gene. A role for this candidate gene in cardiac development was further supported by its conserved expression in the developing human and zebrafish heart. Moreover, a critical, dosage-sensitive role during development was demonstrated by the cardiac defects observed upon titrated knockdown of tab2 expression in zebrafish embryos. To definitively confirm the role of this candidate gene in CHDs, we performed mutation analysis of TAB2 in 402 patients with a CHD, which revealed two evolutionarily conserved missense mutations. Finally, a balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development. PMID:20493459

Relationships between QT interval and heart rate variability at rest and the covariates in healthy young adults.

PubMed

Arai, Kaori; Nakagawa, Yui; Iwata, Toyoto; Horiguchi, Hyogo; Murata, Katsuyuki

2013-01-01

To clarify the links between ECG QT-related parameters and heart rate variability (HRV) and the covariates possibly distorting them, the averaged RR and QT intervals in a single lead ECG were measured for 64 male and 86 female subjects aged 18-26. The QT index, defined by Rautaharju et al., in the young adults was not significantly related to any HRV parameters nor heart rate, but the Bazett's corrected QT (QTc) interval was associated negatively with the parasympathetic activity and positively with heart rate. No significant differences in the QTc interval, QT index or heart rate were seen between the men and women, but they significantly differed between both sexes after adjustment for possible covariates such as age and body mass index (BMI). Significant sex differences in parasympathetic parameters of the HRV were unchanged before and after the adjustment, but significant differences observed in the unadjusted sympathetic parameters disappeared after adjusting for covariates. Age, BMI and body fat percentage also were significant covariates affecting these ECG parameters. Consequently, QT index, unaffected by heart rate and HRV parameters, appears to be a more useful indicator than the QTc interval. Instead, the QT index and HRV parameters are recommended to be simultaneously measured in epidemiological research because they are probably complementary in assessing autonomic nervous function. Also, these parameters should be analyzed in men and women separately. Copyright © 2012 Elsevier B.V. All rights reserved.

The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model

PubMed Central

Melkani, Girish C.; Bodmer, Rolf; Ocorr, Karen; Bernstein, Sanford I.

2011-01-01

UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophila heart model to examine its role in cardiac physiology, in conjunction with RNAi-mediated gene silencing specifically in the heart in vivo. Analysis of cardiac physiology was carried out using high-speed video recording in conjunction with movement analysis algorithms. unc-45 knockdown resulted in severely compromised cardiac function in adults as evidenced by prolonged diastolic and systolic intervals, and increased incidence of arrhythmias and extreme dilation; the latter was accompanied by a significant reduction in muscle contractility. Structural analysis showed reduced myofibrils, myofibrillar disarray, and greatly decreased cardiac myosin accumulation. Cardiac unc-45 silencing also dramatically reduced life-span. In contrast, third instar larval and young pupal hearts showed mild cardiac abnormalities, as severe cardiac defects only developed during metamorphosis. Furthermore, cardiac unc-45 silencing in the adult heart (after metamorphosis) led to less severe phenotypes. This suggests that UNC-45 is mostly required for myosin accumulation/folding during remodeling of the forming adult heart. The cardiac defects, myosin deficit and decreased life-span in flies upon heart-specific unc-45 knockdown were significantly rescued by UNC-45 over-expression. Our results are the first to demonstrate a cardiac-specific requirement of a chaperone in Drosophila, suggestive of a critical role of UNC-45 in cardiomyopathies, including those associated with unfolded proteins in the failing human heart. The dilated cardiomyopathy phenotype associated with UNC-45 deficiency is mimicked

Implantable Heart Aid

NASA Technical Reports Server (NTRS)

1984-01-01

CPI's human-implantable automatic implantable defibrillator (AID) is a heart assist system, derived from NASA's space circuitry technology, that can prevent erratic heart action known as arrhythmias. Implanted AID, consisting of microcomputer power source and two electrodes for sensing heart activity, recognizes onset of ventricular fibrillation (VF) and delivers corrective electrical countershock to restore rhythmic heartbeat.

History of Asthma From Childhood and Arterial Stiffness in Asymptomatic Young Adults: The Bogalusa Heart Study.

PubMed

Sun, Dianjianyi; Li, Xiang; Heianza, Yoriko; Nisa, Hoirun; Shang, Xiaoyun; Rabito, Felicia; Kelly, Tanika; Harville, Emily; Li, Shengxu; He, Jiang; Bazzano, Lydia; Chen, Wei; Qi, Lu

2018-05-01

Asthma is related to various cardiovascular risk. Whether a history of asthma from childhood contributes to arterial stiffness in adulthood, a noninvasive surrogate for cardiovascular events, is unknown. Prospective analyses were performed among 1746 Bogalusa Heart Study participants aged 20 to 51 years with data on self-report asthma collected since childhood. Aorta-femoral pulse wave velocity (af-PWV, m/s) was repeatedly assessed among adults ≥aged 18 years. Generalized linear mixed models and generalized linear models were fitted for the repeated measurements of af-PWV and its changes between the last and the first measurements, respectively. After a median follow-up of 11.1 years, participants with a history of asthma from childhood had a higher af-PWV (6.78 versus 6.13; P =0.048) and a greater increase in af-PWV (8.99 versus 2.95; P =0.043) than those without asthma, adjusted for age, sex, race, smoking status, heart rate, body mass index, systolic blood pressure, lipids, and glycemia. In addition, we found significant interactions of asthma with body mass index and systolic blood pressure on af-PWV and its changes ( P for interaction <0.01). The associations of asthma with af-PWV and its changes appeared to be stronger among participants who were overweight and obese (body mass index ≥25 kg/m 2 ) or with prehypertension and hypertension (systolic blood pressure ≥120 mm Hg) compared with those with a normal body mass index or systolic blood pressure. Our findings indicate that a history of asthma from childhood is associated with higher af-PWV and greater increases in af-PWV, and such associations are stronger among young adults who are overweight or with elevated blood pressure. © 2018 American Heart Association, Inc.

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

Expansion of the Multi-Link Frontier™ Coronary Bifurcation Stent: Micro-Computed Tomographic Assessment in Human Autopsy and Porcine Heart Samples

PubMed Central

Kralev, Stefan; Haag, Benjamin; Spannenberger, Jens; Lang, Siegfried; Brockmann, Marc A.; Bartling, Soenke; Marx, Alexander; Haase, Karl-Konstantin; Borggrefe, Martin; Süselbeck, Tim

2011-01-01

Background Treatment of coronary bifurcation lesions remains challenging, beyond the introduction of drug eluting stents. Dedicated stent systems are available to improve the technical approach to the treatment of these lesions. However dedicated stent systems have so far not reduced the incidence of stent restenosis. The aim of this study was to assess the expansion of the Multi-Link (ML) Frontier™ stent in human and porcine coronary arteries to provide the cardiologist with useful in-vitro information for stent implantation and selection. Methodology/Principal Findings Nine ML Frontier™ stents were implanted in seven human autopsy heart samples with known coronary artery disease and five ML Frontier™ stents were implanted in five porcine hearts. Proximal, distal and side branch diameters (PD, DD, SBD, respectively), corresponding opening areas (PA, DA, SBA) and the mean stent length (L) were assessed by micro-computed tomography (micro-CT). PD and PA were significantly smaller in human autopsy heart samples than in porcine heart samples (3.54±0.47 mm vs. 4.04±0.22 mm, p = 0.048; 10.00±2.42 mm2 vs. 12.84±1.38 mm2, p = 0.034, respectively) and than those given by the manufacturer (3.54±0.47 mm vs. 4.03 mm, p = 0.014). L was smaller in human autopsy heart samples than in porcine heart samples, although data did not reach significance (16.66±1.30 mm vs. 17.30±0.51 mm, p = 0.32), and significantly smaller than that given by the manufacturer (16.66±1.30 mm vs. 18 mm, p = 0.015). Conclusions/Significance Micro-CT is a feasible tool for exact surveying of dedicated stent systems and could make a contribution to the development of these devices. The proximal diameter and proximal area of the stent system were considerably smaller in human autopsy heart samples than in porcine heart samples and than those given by the manufacturer. Special consideration should be given to the stent deployment procedure (and to the follow-up) of dedicated

Nationwide survey of care facilities for adults with congenital heart disease in Japan.

PubMed

Toyoda, Tomohiko; Tateno, Shigeru; Kawasoe, Yasutaka; Shirai, Takeaki; Shiina, Yumi; Matsuo, Kozo; Niwa, Koichiro

2009-06-01