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There are in excess of one million people across the UK people living with atrial fibrillation (AF), a long term condition that can lead to stroke and other complications, costing the NHS over £2,200 million per year. However little is known about the experience of living with AF and what patients' perceptions are of the support they receive from health professionals. In order to ensure that patients have the best possible experience of care, healthcare professionals need to have an understanding of how patients view their condition and the type of support they would like to receive from the professionals involved in their care. Although there has been a significant amount of work investigating social support for people with health conditions, there has been little work exploring support provided by healthcare professionals, defined in this study as professional support. This study aimed to investigate and assess the professional support needs of people with AF to develop knowledge and understanding in this field. A theoretical framework for professional support was developed based on the tri-dimensional model of social support and was used to direct the research. Using an exploratory sequential design, a two phase mixed methods study was undertaken. Initially, qualitative interviews were undertaken with patients recruited from outpatient arrhythmia clinics at one National Health Service (NHS) hospital and identified from the perspective of the patient how, when and where healthcare professionals did/did not provide support. Key components of emotional, informational and tangible professional support were identified from thematic analysis of the interview data and used to inform the development of a quantitative questionnaire. Physical activity, exercise and the impact of AF on activity levels were identified by participants as important and so were also included. The quantitative online questionnaire was completed by patient members of the Atrial Fibrillation Association (AFA). To examine relationships between variables, statistical analyses were performed using Fisher's exact test and indicated that people with AF had a range of emotional, informational and tangible professional support needs. Different subgroups of people with AF had different professional support needs: People with more severe symptoms needed more emotional support as well as more tangible support and people with paroxysmal AF needed more informational support. People undergoing ablation as treatment for their AF had specific informational and emotional needs for support. AF played a significant part in the lives of people with AF by modifying activities of daily living and shaping physical activity behaviour and choice of activities. People with AF therefore needed professional support in maintaining and/or increasing their levels of activity. Considering the specificity of professional support, GPs, cardiologists and arrhythmia nurse specialists were identified as most supportive, with GPs and cardiologists also considered as the least helpful at providing support, indicating a variation in professional support. The findings from this study contribute to the limited body of knowledge describing the experience of living with AF and provide healthcare professionals with a unique understanding of how best to provide professional support. The tri-dimensional model provides detailed knowledge of the components of informational, emotional and tangible support that people with AF would like to receive from the healthcare professionals involved in their care. The findings indicate there are differing support needs for different subsets of people with AF demonstrating a need for individualised professional support. The theoretical framework for professional support used in this study provides a model that could be used in future research studies to identify the types of professional support required by patients and to identify subgroups of patients who may require additional professional support. By accurately identifying the needs of patients, this will ensure that healthcare professionals are able to deliver effective patient centred services, leading to an improved patient experience and the delivery of high quality patient care.

Memoria para optar al Título Profesional de Médico Veterinario / Antecedentes de la investigación. Las species reactivas de oxígeno (ERO), estarían involucradas en la producción de modificaciones estructurales y eléctricas, que hacen susceptible al tejido auricular a arritmias y disfunción contráctil. Por lo tanto, un reforzamiento del sistema de defensa antioxidante protegería al corazón del daño hipóxico generado por las especies reactivas al oxigeno en la cirugía cardiaca no congénita con circulación extracorpórea. Hipotesis. En pacientes sometidos a cirugía de cardiopatías no congénitas, la suplementación previa con acidos grasos omega-3 y vitaminas antioxidantes C y E, reduce la ocurrencia de fibrilación auricular postoperatoria (FAPO). Métodos. En un ensayo clínico doble-ciego, se separaron al azar 90 pacientes en dos grupos, a placebo o von una dosis diaria de omega 3, desde 7 días previos a la cirugía programada. Dos días antes de la cirugía se adicionó la suplementación de vitaminas (C y E). Estos 3 suplementos/placebos se administraron en forma ininterrumpida hasta el alta. Se obtuvieron muestras de sangre: previo a la incorporación de las vitaminas antioxidantes, al momento de la intervención quirúrgica, y postoperatoria temprana para la determinación del estatus antioxidante (relación glutatión reducido (GSH)/oxidado (GSSG), enzimas antioxidantes) y del estatus proxidante (biomarcadores de estrés oxidativo (malondialdehido y carbonilación proteica). En el acto quirúrgico se obtuvo tejido auricular (orejuela derecha) conservado en nitrógeno para su posterior análisis bioquímico del estatus antioxidante/proxidante. Se compararon a través del test de Student y el estudio de correlaciones se realizo de acuerdo al test de Pearson. Resultados. El uso de omega-3 y vitaminas antioxidantes atenuarían el daño oxidativo, logrando con la suplementación bajo este protocolo, una disminución en un 68,5% de la FAPO, junto con menores valores de biomarcadores de estrés oxidativo tanto en eritrocitos como en el tejido auricular, sumado a un mayor nivel de relación Glutatión (GSH/GSSG) en eritrocitos y mayor respuesta al estrés oxidativo de Superóxido dismutasa (SOD) eritrocitaria postoperatoria temprano y Glutatión peroxidasa (GSH-Px) operatoria en tejido auricular principalmente. Conclusiones. La suplementación con omega-3 y vitaminas antioxidantes atenúa el daño oxidativo en pacientes sometidos a cirugía cardíaca con CEC. Evidenciando posterior a la cirugía en el grupo suplementado una mayor actividad enzimática, in aumento de la relación de glutatión, y menores índices de biomarcadores de estrés oxidativo / Fondecyt: 1070948

The aim of this thesis was to describe and explore how the partner relationship of patient–partner dyads isaffected following cardiac disease and, in particular, atrial fibrillation (AF) in one of the spouses. The thesis is based on four individual studies with different designs: descriptive (I), explorative (II, IV), and cross-sectional (III). Applied methods comprised a systematic review (I) and qualitative (II, IV) and quantitative methods (III). Participants in the studies were couples in which one of the spouses was afflicted with AF. Coherent with a systemic perspective, the research focused on the dyad as the unit of analysis. To identify and describe the current research position and knowledge base, the data for the systematic review were analyzed using an integrative approach. To explore couples’ main concern, interview data (n=12 couples) in study II were analyzed using classical grounded theory. Associations between patients and partners (n=91 couples) where analyzed through the Actor–Partner Interdependence Model using structural equation modelling (III). To explore couples’ illness beliefs, interview data (n=9 couples) in study IV were analyzed using Gadamerian hermeneutics. Study I revealed five themes of how the partner relationship is affected following cardiac disease: overprotection, communication deficiency, sexual concerns, changes in domestic roles, and adjustment to illness. Study II showed that couples living with AF experienced uncertainty as the common main concern, rooted in causation of AF and apprehension about AF episodes. The theory of Managing Uncertainty revealed the strategies of explicit sharing (mutual collaboration and finding resemblance) and implicit sharing (keeping distance and tacit understanding). Patients and spouses showed significant differences in terms of self-reported physical and mental health where patients rated themselves lower than spouses did (III). Several actor effects were identified, suggesting that emotional distress affects and is associated with perceived health. Patient partner effects and spouse partner effects were observed for vitality, indicating that higher levels of symptoms of depression in patients and spouses were associated with lower vitality in their partners. In study IV, couples’ core and secondary illness beliefs were revealed. From the core illness belief that “the heart is a representation of life,” two secondary illness beliefs were derived: AF is a threat to life, and AF can and must be explained. From the core illness belief that “change is an integral part of life,” two secondary illness beliefs were derived: AF is a disruption in our lives, and AF will not interfere with our lives. Finally, from the core illness belief that “adaptation is fundamental in life,” two secondary illness beliefs were derived: AF entails adjustment in daily life, and AF entails confidence in and adherence to professional care. In conclusion, the thesis result suggests that illness, in terms of cardiac disease and AF, affected and influenced the couple on aspects such as making sense of AF, responding to AF, and mutually incorporating and dealing with AF in their daily lives. In the light of this, the thesis results suggest that clinicians working with persons with AF and their partners should employ a systemic view with consideration of couple’s reciprocity and interdependence, but also have knowledge regarding AF, in terms of pathophysiology, the nature of AF (i.e., cause, consequences, and trajectory), and treatments. A possible approach to achieve this is a clinical utilization of an FSN based framework, such as the FamHC. Even if a formalized FSN framework is not utilized, partners should not be neglected but, rather, be considered a resource and be a part of clinical caring activities. This could be met by inviting partners to take part in rounds, treatment decisions, discharge calls or follow-up visits or other clinical caring activities. Likewise, interventional studies should include the couple as a unit of analysis as well as the target of interventions.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, occurring in 1% of the adult population of North America. Although AF does not typically lead to risk of immediate mortality, it is a potent risk factor for ischemic stroke. When left untreated AF reduces quality of life, functional status, cardiac performance and is associated with higher medical costs and an increased risk of death. Catheter ablation is a commonly used treatment method for those who suffer from drugrefractory AF. Prior to ablation, intra-cardiac mapping can be used to determine the activation sequence of cardiac tissue, which may be useful in deciding where to place ablation lesions. However, the electrical potential that is recorded during mapping is not a direct reflection of the current density across the tissue because the potential recorded at each point above the heart tissue is influenced by every cell in the tissue. This causes the recorded potential to be a blurred version of the true tissue current density. The potential that is observed can be described as the convolution of the true current density with a point spread function. Accordingly, deconvolution can, in principle, be used in order to improve the resolution of potential maps. However, because the number of electrodes which can be deployed transvenously is limited by practical restrictions, the recorded potential field is a sparsely sampled version of the actual potential field. Further, an electrode array cannot sample over the entire atrial surface, so the potential map that is observed is a truncated version of the global electrical activity. Here, we investigate the effects of electrode sampling density and edge extension on the ability of deconvolution to improve the resolution of measured electrical potentials within the atria of the heart. In particular, we identify the density of sensing electrodes that are required to allow deconvolution to provide improved estimation of the true current density when compared to the observed potential field.

by Ngai Wing Keung Clement. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 172-206). / Chapter 1. --- Acknowledgment --- p.iv / Chapter 2. --- Abstract --- p.v / Chapter 3. --- Lists of Tables and Figures --- p.vii / Chapter 4. --- General Introduction --- p.1 / Chapter 5. --- Review of Literature --- p.5 / Chapter 5.1. --- Historical Background of Natriuretic Peptides --- p.5 / Chapter 5.2. --- Secretion of Natriuretic Peptides --- p.8 / Chapter 5.3. --- Structure and Function Relationships --- p.12 / Chapter 5.4. --- Physiological Actions --- p.17 / Chapter 5.5. --- Natriuretic Peptide Receptors and Second Messengers --- p.22 / Chapter 5.6. --- Clinical Implications --- p.28 / Chapter 5.7. --- Review on Astrocytes --- p.31 / Chapter 6. --- General Materials and Methods --- p.43 / Chapter 6.1. --- Sources of Chemicals --- p.43 / Chapter 6.2. --- Culture of Mouse Astrocytes --- p.43 / Chapter 6.3. --- Culture of human astrocytoma cells --- p.57 / Chapter 6.4. --- Protein Determination --- p.57 / Chapter 6.5. --- Gamma Counting --- p.58 / Chapter 6.6. --- Beta Counting --- p.58 / Chapter 7. --- Receptor Identification and Characterization --- p.59 / Chapter 7.2 --- Materials and Methods --- p.60 / Chapter 7.3 --- Results --- p.66 / Chapter 7.4 --- Discussion --- p.81 / Chapter 8. --- Second Messenger Systems --- p.83 / Chapter 8.1 --- Introduction --- p.83 / Chapter 8.2 --- Materials and Methods --- p.85 / Chapter 8.3 --- Results --- p.97 / Chapter 8.4 --- Discussion --- p.109 / Chapter 9. --- Biological Actions of Natriuretic Peptides --- p.113 / Chapter 9.1. --- Potassium Transport --- p.113 / Chapter 9.1.1. --- Introduction --- p.113 / Chapter 9.1.2. --- Materials and Methods --- p.116 / Chapter 9.1.3. --- Results --- p.121 / Chapter 9.1.4. --- Discussion --- p.131 / Chapter 9.2 --- Taurine Release --- p.135 / Chapter 9.2.1. --- Introduction --- p.135 / Chapter 9.2.2. --- Materials and Methods --- p.137 / Chapter 9.2.3. --- Results --- p.139 / Chapter 9.2.4. --- Discussion --- p.143 / Chapter 9.3 --- Thymidine Incorporation --- p.144 / Chapter 9.3.1. --- Introduction --- p.144 / Chapter 9.3.2. --- Materials and Methods --- p.146 / Chapter 9.3.3. --- Results --- p.148 / Chapter 9.3.4. --- Discussion --- p.156 / Chapter 10. --- Interaction with Other Hormonal Systems --- p.160 / Chapter 10.1 --- Introduction --- p.160 / Chapter 10.2 --- Materials and Methods --- p.162 / Chapter 10.3 --- Result --- p.163 / Chapter 10.4 --- Discussion --- p.167 / Chapter 11. --- Conclusion --- p.169 / Chapter 12. --- References --- p.172 / Chapter 13. --- Appendix --- p.208

The interaction between the mapping/ablation catheter and left atrial (LA) myocardium potentially affects the LA electrical and mechanical properties and impacts on ablation efficacy. Using catheters able to provide real-time contact force (CF) measurement, it has become possible to explore these relationships in vivo. In 60 persistent atrial fibrillation (AF) patients, ablation CF was higher in the right than left wide area circumferential (WACA) lines and where steerable transseptal sheaths were used. Differences were also apparent in the burden of WACA segment reconnection but did not just reflect differences in ablation CFs, suggesting factors other than CF contribute to ablation efficacy. Relationships between ablation force time integral (FTI), impedance drop and electrogram attenuation were assessed in 15 persistent AF patients. FTI significantly correlated with electrogram attenuation and impedance drop from ablation. The relationship was stronger for the former but in both cases plateaued at 500g.s, suggesting no ablation efficacy gains beyond this. Factors further affecting CF and ablation efficacy, the latter judged by impedance drop, were assessed in 30 patients. The variability of the CF waveform and catheter locational stability were both affected by factors including atrial rhythm and catheter delivery mode. Greater CF variability, catheter drift and perpendicular catheter contact were associated with reduced ablation efficacy. The relationship between CF and the electrogram was assessed in 30 patients. The size of the electrogram complexes was affected by CF increases but only where initial CF was <10g. This was also the case for electrogram fractionation measurements. Increasing CF was associated with an increasing incidence of atrial ~ 3 ~ ectopics during sinus rhythm. Spectral parameters (dominant frequency and organisation index) were unaffected by CF. Various factors affect the contact between the catheter and LA myocardium. In turn, catheter contact significantly affects the electrogram during LA mapping and the efficacy of clinical radiofrequency ablation.

BACKGROUND: Atrial Fibrillation (AF) is the most common cardiac arrhythmia, affecting over 3 million Americans. Many people who suffer from AF have pre-disposing factors such as hypertension, ischemia, and structural heart disease, but recent research has also demonstrated the importance of genetic factors that can contribute to AF. In the present study, we sought to determine the causative mutation in a family with AF, atrial septal, and ventricular septal defects. METHODS: We evaluated a pedigree with 16 family members, one of whom had an ASD, one a VSD, and three had AF. Exome sequencing was performed on three of the five affected family members followed by confirmation with Sanger sequencing in all family members. A separate cohort from the MGH AF Study with early-onset AF (age at onset 47.1 ± 10.9 years, 79.3% male) was also screened for mutations using a combination of Sanger sequencing and high resolution melting. Variants were then functionally characterized using reporter assays in a mammalian cell line using wild-type and mutant constructs driving NPPA, αMHC and NPPB promoter reporters. RESULTS: Exome sequencing of the three affected individuals in the family identified a highly conserved mutation, R585L, in the transcription factor gene, GATA6. We also identified three additional GATA6 variants (P91S, A177T, and A543G) in the cases with early-onset AF from the MGH AF Study. We found that three of the four variants had a marked upregulation of luciferase activity (R585L; 4.1 fold, p<0.0001; P91S; 2.5 fold, p=0.0002; A177T; 1.7 fold, p=0.03). Additionally, when co-overexpressed with GATA4 and MEF2C, all GATA6 variants exhibited upregulation of the αMHC and NPPA activity compared to control. CONCLUSION: Overall, we found gain-of-function mutations in GATA6 in both a family with early-onset AF and atrioventricular septal defects as well as in patients with sporadic, early-onset AF. This evidence suggests that specific gain of function mutations in GATA6 contribute to the development of AF. / 2017-06-16T00:00:00Z