Background: Cardiac Rehabilitation (CR) has been shown to be effective in reducing mortality and morbidity in Coronary Heart Disease (CHD). There is a limited amount of research that evaluates the impact of menu-based CR, in patients with Acute Coronary Syndrome with Low Troponin levels (ACSLT). Aim: This thesis contains a feasibility study and an exploratory study. The feasibility study aimed to examine the feasibility of a Randomised Controlled Trial (RCT) which would test the impact of a menu-based CR programme, on individuals diagnosed with ACSLT, against standard care. This feasibility study included staff views. The exploratory study aimed to explore the impact that ACSLT and CR can have on this client group. Method: The feasibility study was a repeated measures case-control trial of menu-based CR based on the theoretical framework of the Common Sense Model of Self-Regulation (CSM), using a range of health assessments. The areas assessed included misconceptions, symptoms, anxiety, depression and Health Related Quality of Life (HRQoL). In addition, focus groups were held with both ward and specialist CR staff to seek their views on the feasibility of a RCT of menu-based CR for ACSLT. The exploratory study consisted of description and analysis of the data that had been collected from the participants over the two year period as above. In addition it included qualitative data that had been collected during interviews with the participants. Findings: Participants (n=33) were recruited from cardiology wards following an admission with ACSLT. They were assessed at baseline (T1), nine months (T3) and 24 months (T4). Twenty-five participants completed the studies. The feasibility study was successful in its aim of testing the CR intervention and protocols for a further RCT. The intervention was acceptable to the participants and to the specialist staff, although the ward staff did not see the need for a RCT. The measures used, with the exception of the self-reporting measures, were suitable and provided a wide range of data that could be utilised in a RCT. However the changes to diagnostic categories meant that a RCT would no longer be feasible. The exploratory study found that both groups were similar on a range of baseline demographic and clinical factors. There was a tendency to benefit within the exploratory study which favoured the intervention. An additional finding from the exploratory study was the degree of uncertainty experienced by the participants, within the context of a changing political and clinical landscape. Discussion and conclusions: The studies presented in this thesis add to our knowledge by highlighting some of the difficulties in designing a RCT of menu-based CR in a specific subgroup of CHD and by presenting outcome data for a small group of participants that have not previously been studied within the literature. This data suggests that there was a tendency to benefit for the intervention that requires further study. Implications for practice: Patients with ACSLT are now being included in CR programmes due to the changes within the diagnostic criteria. Clinicians have little understanding of the impact of CR on this group of patients, or what type of interventions would work best. Large RCT’s will however be problematic and this thesis has highlighted that further work is required to explore how CR can best improve the well-being of individuals with ACSLT.

Les gènes Hox sont essentiels à la mise en place de l’identité des cellules le long de l’axe antéropostérieur des embryons et pourraient agir en aval de l’acide rétinoïque pendant la formation du cœur. Nous montrons que les gènes Hoxb1, Hoxa1 et Hoxa3 définissent des sous-domaines du second champ cardiaque. L’analyse de lignage génétique révèle que les progéniteurs cardiaques Hoxb1+ contribuent aux oreillettes et à la partie inférieure de la voie efférente, futur myocarde sous-pulmonaire. Les progéniteurs Hoxa1+ contribuent à la partie distale de la voie efférente, suggérant un rôle de ces gènes Hox antérieurs dans sa régionalisation proximo-distale. Alors qu’aucune anomalie cardiaque n’avait été décrite chez les mutants Hoxb1, notre étude détaillée des fœtus Hoxb1-/- révèle des défauts d’alignement des gros vaisseaux ainsi que des communications interventriculaires. L’utilisation d’un marqueur du myocarde sous-pulmonaire, montre une contribution anormale des cellules du second champ cardiaque à cette région chez les mutants. Nous montrons que ces défauts sont la conséquence de la dérégulation des voies de signalisation présentes dans le second champ cardiaque. En accord avec ces observations, les embryons ont une voie efférente plus courte. L’étude des mutants Hoxa1 révèle des malformations des arcs pharyngés puis des anomalies de la crosse aortique chez les fœtus. L’analyse des doubles mutants, montre une augmentation de la pénétrance et de la sévérité de ces défauts, suggérant une interaction synergique entre Hoxa1 et Hoxb1 lors de la formation des gros vaisseaux. Ces résultats révèlent un rôle crucial des gènes Hox antérieurs dans le développement du cœur. / Hox genes are known to be involved in the establishment of cell position and identity along the anterior-posterior axis in embryos and could act as key downstream effectors of retinoic acid during heart development. In situ hybridization experiments show that Hoxb1, Hoxa1 and Hoxa3 define sub-domains within the second heart field (SHF). Our genetic lineage analysis reveals the contribution of Hoxb1+ cardiac progenitors to the atria and to the inferior wall of the outflow tract (OFT), which then gives rise to the myocardium at the base of the pulmonary trunk. Interestingly, Hoxa1+ progenitors contribute to the distal part of the OFT suggesting that these anterior Hox genes could play a role in its proximo-distal patterning. No cardiac anomalies had been reported so far in Hoxb1 mutant mice. However, our detailed study shows that mutant fetuses exhibit OFT misalignment and ventricular septal defects associated or not with ventricular wall and epicardium anomalies. Using a marker of the sub-pulmonary myocardium, we observe an abnormal contribution of SHF cells in Hoxb1-/- hearts. This defect is the consequence of the dysregulation of the signaling pathways controlling SHF regulation. Accordingly, those embryos exhibit a shorter OFT. The study of Hoxa1 mutant embryos reveals pharyngeal arch arteries patterning defects causing anomalies of the aortic arch and right subclavian artery at fetal stages. Using compound mutants, we show an increase in the penetrance and severity of these defects, suggesting a synergistic interaction between Hoxa1 and Hoxb1 during aortic arch patterning. Together, these data support a crucial role for anterior Hox genes in cardiac development.

Bakgrund: Hjärt-och kärlsjukdomar är den vanligaste dödsorsaken i världen. En behandlingsform som skyddar mot hjärt-och kärlsjukdomar i form av plötslig hjärtdöd och livshotande arytmier är en Implanterbar Cardioverter Defibrillator (ICD). ICD-apparaten kan bland annat avge defibrilleringar när hjärtats rytm avviker från normal sinusrytm. Hälsorelaterad livskvalitet kan mätas för att avgöra hur en viss behandling påverkar människors livskvalitet. Hälsorelaterad livskvalitet kan mätas med hjälp av olika mätskalor. Skalorna undersöker bland annat patienters hälsostatus, emotionell och psykisk funktion och hur dessa påverkar det sociala och dagliga livet. Begreppet kan även brytas ner till olika domäner i form av generell livskvalitet samt psykiska domän i form av depression och ångest. Syfte: Syftet med litteraturstudien var att undersöka hur ICD-behandlingen påverkar den hälsorelaterade livskvaliteten hos personer med en implanterbar ICD. Metod: En litteraturstudie med kvantitativ ansats tillämpades och baserades på tolv vetenskapliga artiklar. Resultat: Den hälsorelaterade livskvaliteten hos hjärtsjuka patienter inför en ICD-behandling var signifikant försämrad, i jämförelse med generell befolkning. Den rapporterade livskvaliteten hos hjärtsjuka människor uppmättes som lägst kort innan en ICD-implantation och ICD-behandlingen utgav en signifikant förbättring på livskvaliteten, sex till tolv månader efter implantionen. Ångestrelaterade tankar, depression, den emotionella, psykiska och mentala hälsan angav förbättrade resultat när patienterna fått ICD-behandling, i jämförelse med hur den hälsorelaterade livskvaliteten hos patienterna var före behandlingen. Konklusion: Den hälsorelaterade livskvaliteten tenderade att höjas hos hjärtsjuka patienter som fått en implanterad ICD. Utan ICD-behandling uppmätte hjärtsjuka patienter en signifikant försämrad livskvalitet, i jämförelse med generell befolkning. Däremot försvann den signifikanta skillnaden i hälsorelaterad livskvaliteten mellan hjärtsjuka patienter och generell befolkning efter att de hjärtsjuka erhållit en ICD-behandling. / Background: Heart-diseases are the most common cause of death in the whole world. Treatment that could possibly save patients from sudden cardiac arrest and life-threatening arrhythmias is the Implantable Cardioverter Defibrillator (ICD). The ICD can for instance give defibrillations when the heart departs from regular sinus rhythm. Health-related quality of life can be measured to assess how a certain treatment is affecting peoples’ quality of life. ICD-treatment can be measured in health-related quality of life. Health-related quality of life can be measured with help of different types of measurements and scales. It investigates the patients’ health-status and physical and emotional function and in which way it impacts the daily and social life. Health-related quality of life is a huge concept that can be divided in to smaller domains, like general quality of life and physical symptoms like depression and anxiety. Aim: The aim of this study was to investigate how ICD-treatment infects patients’ health-related quality of life.Method: A literature review with quantitative study-design, based on twelve scientific articles. Result: The health-related quality of life in patients with cardiac problems who are facing an ICD-treatment were significant worse, in comparison with the general population. However, the reported quality of life in patients with cardiac problems was measured at its lowest shortly before the ICD-implantation and the ICD-treatment had a significant improvement on the quality of life, six to twelve months after the implantation. Anxiety-related thoughts, depression, the emotional, physical and mental health indicated a better result when the patients with cardiac problems received an implantable ICD, in comparison with how the health-related quality of life were before the treatment. Conclusion: The health-related quality of life tends to increase after the patients with cardiac problems received an ICD. Without the ICD-treatment, the patients with cardiac problems measure a significantly worse quality of life, in comparison to the general population. However, the significantly worse impact on the quality of life in patients with cardiac problems in comparison with the general population, disappeared after the patients received an ICD.

Indiana University-Purdue University Indianapolis (IUPUI) / The epidemic of obesity and associated cardiovascular complications continues to grow at an alarming rate. Currently, obesity is thought to initiate a state of chronic inflammation, which if unresolved potentially causes cardiovascular dysfunction and disease. Although poorly understood, release of inflammatory mediators and other cytokines from adipose tissue (adipocytokines) has been proposed to be the molecular link between obesity and coronary artery disease. Furthermore, the anatomic location of adipose has been increasingly recognized as a potential contributor to vascular disease. Importantly, the development of coronary atherosclerosis, a key component of heart disease, is typically found in segments of coronary arteries surrounded by perivascular adipose tissue. Accordingly, the goal of this project was to determine how perivascular adipose tissue affects coronary artery function and elucidate the critical mechanisms involved. Initial studies assessing arterial function were conducted with and without perivascular adipose tissue. Preliminary results demonstrated that factors released by perivascular adipose tissue effectively impaired coronary endothelial function both in vitro and in vivo. This observation was determined to be caused by direct inhibition of nitric oxide synthase (NOS), a critical enzyme for the production nitric oxide. Attenuation of endothelium-dependent vasodilation was independent of changes in superoxide production, smooth muscle response, or peroxide-mediated vasodilation. Additional studies revealed that perivascular adipose-induced impairment of NOS was due to increased inhibitory regulation by the β isoform of protein kinase C (PKC-β). Specifically, perivascular adipose-derived factors caused site specific phosphorylation of nitric oxide synthase at Thr-495. Additional experiments investigated how perivascular adipose-derived factors contributed to coronary artery disease in an animal model of obesity. Results from these studies indicated that perivascular adipose-derived leptin markedly exacerbated underlying endothelial dysfunction, and significantly contributed to coronary endothelial dysfunction through a PKC-β dependent mechanism. Findings from this project confirm epicardial perivascular adipose tissue as a local source of harmful adipocytokines. In addition, perivascular adipose-derived leptin was demonstrated to be a critical mediator of coronary vascular dysfunction in obesity. Together, the results strongly suggest that perivascular adipose tissue is a key contributor to coronary artery disease in obesity.

This qualitative study sought to explore the Hong Kong Chinese patient's perceptions of an Intensive Care experience and their views on the introduction of feng shui principles focussing on sleep orientations, dietary management and exercise regimes. The study explored the background of feng shui as an authentic traditional Chinese belief. It also explores if incorporating these feng shui principles into the health care setting would provide a positive effect for open-heart patients in an Intensive Care Unit at the Hong Kong Adventist Hospital in Hong Kong. The major inference drawn from this study is that Chinese patients seek culturally related experiences from the health care setting. The Chinese informants showed strong belief patterns in traditional practices of feng shui, however, practiced these within the confines of their homes as these experiences were denied to them in the hospital setting. / Health Studies / M.A. (Nursing Science)

This qualitative study sought to explore the Hong Kong Chinese patient's perceptions of an Intensive Care experience and their views on the introduction of feng shui principles focussing on sleep orientations, dietary management and exercise regimes. The study explored the background of feng shui as an authentic traditional Chinese belief. It also explores if incorporating these feng shui principles into the health care setting would provide a positive effect for open-heart patients in an Intensive Care Unit at the Hong Kong Adventist Hospital in Hong Kong. The major inference drawn from this study is that Chinese patients seek culturally related experiences from the health care setting. The Chinese informants showed strong belief patterns in traditional practices of feng shui, however, practiced these within the confines of their homes as these experiences were denied to them in the hospital setting. / Health Studies / M.A. (Nursing Science)

Background: Beta blockers are recommended by the American College of Cardiology/American Heart Association Guidelines for high and intermediate-risk cardiac patients undergoing non-cardiac surgery. Beta blockers are a class of drugs that moderate the effects of increased catecholamine levels on the heart by selectively blocking beta receptors in the heart and blood vessels, resulting in a lower heart rate and blood pressure. Beta blocker use perioperatively has been shown to reduce the risk of ischemia and infarction. Purpose: The purpose of this project is to address beta blocker use in a group of anesthesia providers who routinely attend to high-risk and intermediate-risk cardiac patients undergoing non-cardiac surgery in a medium-sized private hospital in suburban South Florida. There are barriers to the implementation of the published guidelines for beta blocker administration, including lack of awareness of the best current practice and a lack of a formal beta blocker protocol at the institutional level. Methods: A simple and inexpensive beta blocker protocol was implemented and evaluated by various means. Beta blocker administration practices were examined and documented prior to and after protocol implementation. Beta blocker usage was examined prior to and after protocol implementation Findings/Implications: It was hypothesized that increased anesthesia provider awareness would lead to increased administration of perioperative beta blockers to high-risk and intermediate-risk cardiac patients undergoing non-cardiac procedures. Although there was a knowledge increase related to the new beta blocker protocol, no change in practice was observed.

Indiana University-Purdue University Indianapolis (IUPUI) / Autonomic innervation of the heart begins in utero and continues during the neonatal phase of life. A balance between the sympathetic and parasympathetic arms of the autonomic nervous system is required to regulate heart rate as well as the force of each contraction. Our lab studies the development of sympathetic innervation of the early postnatal heart in a conditional knockout (cKO) of Src homology protein tyrosine phosphatase 2 (Shp2). Shp2 is a ubiquitously expressed non-receptor phosphatase involved in a variety of cellular functions including survival, proliferation, and differentiation. We targeted Shp2 in post-migratory neural crest (NC) lineages using our novel Periostin-Cre. This resulted in a fully penetrant mouse model of diminished cardiac sympathetic innervation and concomitant bradycardia that progressively worsen. Shp2 is thought to mediate its basic cellular functions through a plethora of signaling cascades including extracellular signal-regulated kinases (ERK) 1 and 2. We hypothesize that abrogation of downstream ERK1/2 signaling in NC lineages is primarily responsible for the failed sympathetic innervation phenotype observed in our mouse model. Shp2 cKOs are indistinguishable from control littermates at birth and exhibit no gross structural cardiac anomalies; however, in vivo electrocardiogram (ECG) characterization revealed sinus bradycardia that develops as the Shp2 cKO ages. Significantly, 100% of Shp2 cKOs die within 3 weeks after birth. Characterization of the expression pattern of the sympathetic nerve marker tyrosine hydroxylase (TH) revealed a loss of functional sympathetic ganglionic neurons and reduction of cardiac sympathetic axon density in Shp2 cKOs. Shp2 cKOs exhibit lineage-specific suppression of activated pERK1/2 signaling, but not of other downstream targets of Shp2 such as pAKT (phosphorylated-Protein kinase B). Interestingly, restoration of pERK signaling via lineage-specific expression of constitutively active MEK1 (Mitogen-activated protein kinase kinase1) rescued TH-positive cardiac innervation as well as heart rate. These data suggest that the diminished sympathetic cardiac innervation and the resulting ECG abnormalities are a result of decreased pERK signaling in post-migratory NC lineages.

Timely management in pre-hospital emergency care enhances the chances of patients' survival or clinical outcomes of an Acute Coronary Syndrome (ACS). In Botswana nurses serve in the frontline of pre-hospital emergency services as the initial recipients of the emergency reports and situations. Knowledge of the patient's characteristics will assist the nurses as well as the family/others to understand the patient's responses during an ACS situation and therefore enable prompt patient assessment and facilitation of early access to appropriate care. Patient and family involvement in care during cardiac emergencies also influences the patient outcomes. This is a non-experimental, quantitative, exploratory and descriptive study, designed to explore and describe the characteristics of patients with the experience of an ACS, and the available resources during the pre-hospital phase of emergency care, with the aim of improving patients' clinical outcomes. The results indicated that optimal care by nurses is essential in the chain of care influencing patients' chances of surviving ACS. / Health Studies / M.A. (Health Studies)

A quantitative research design for a descriptive and contextual study to determine the critical care nurses knowledge and data preferences regarding the central venous and pulmonary artery catheters management and decision making after coronary arte.y bypass graft operations and the utmzation period of the pulmonary artery catheter after coronary artery bypass graft operations. The data was collected through a questionnaire completed by critical care nurses and retrospective analysis of patient records through a structured checklist. Data analysis indicated the following: critical care nurses have a knowledge deficit in the management of the central venous and pulmonary artery catheters and felt more competent and confident in the central venous measurements. The utilization period of the pulmonary artery catheter was 48% compared to the 100% of the central venous catheter. / Advanced Nursing Science / M.A. (Advanced Nursing Science)