1,721,237 research outputs found
Aggressive Risk Factor Reduction Study for Atrial Fibrillation (ARREST-AF)
Full text linkAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with evidence from epidemiological data confirming the emergence of AF as a global epidemic. Although population ageing is regarded as an important contributor, several risk factors such as hypertension, diabetes mellitus, obesity, and obstructive sleep apnoea have been epidemiologically linked as promoters of AF. Cardiac risk factors are associated with structural and electrical remodeling of the atria that form the substrate leading to the development and progression of AF. Evidence from animal studies suggests that management of these risk factors such as obesity can reverse some of these changes. This was associated with reduced vulnerability of AF. However, impact of risk factor management on atrial fibrillation in human has not been evaluated. Furthermore, mechanism and degree of reversibility of substrate in humans, where multiple factors can play a role, with weight and other risk factor management has not been described. This thesis evaluates the reversal of atrial substrate with weight and other risk factor management and its impact on AF freedom and AF ablation outcome. Chapter 2 assesses the long-term impact of weight-loss and weight-fluctuation on rhythm control in obese individuals with AF. In over-weight and obese individuals with symptomatic AF, progressive weight-loss had a dose-dependent effect on long-term freedom from AF. Additionally, weight-fluctuation of >5% had an adverse effect on overall freedom from AF with a two-fold greater likelihood of recurrent arrhythmia. Chapter 3 evaluated the impact of cardiorespiratory fitness on long-term freedom from atrial fibrillation (AF). It also looked at the impact of cardiorespiratory fitness gain on AF outcome. This study demonstrates that in overweight and obese individuals with symptomatic AF, preserved baseline cardiorespiratory fitness predicts long-term freedom from AF. Cardiorespiratory fitness gain with a structured exercise program had an additive effect to weight-loss in improving the long-term outcome of AF. Chapter 4 evaluated the impact of aggressive risk factor management on the outcomes of the catheter ablation. In patients with symptomatic AF undergoing ablation, a structured physician-directed risk factor and weight management program resulted in significant improvement in the long-term outcomes. Chapter 5 evaluated the impact of risk factor management on the electrophysiological and electroanatomical properties of the atria, cardiac structure and endothelial and platelets function. Aggressive risk factor management was associated with marked structural improvement with a reduction in atrial size, regression of ventricular mass and normalization of bipolar voltages. There was a resultant significant improvement in the electrophysiological properties with marked improvement in conduction properties and tissue refractoriness. Mechanistically, there was a reduction in pericardial fat volumes and serum fibrosis markers. Furthermore, there was improvement in endothelial function, platelet function and inflammatory markers. These changes were associated with significant reduction in the AF vulnerability and clinical burden of AF. Chapter 6 evaluated the cost effectiveness of a goal dedicated physician led clinic on the outcomes of the catheter ablation. This program is not only clinically effective but also cost-effective in terms of improvement in QALYs and reduction in AF burden.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201
Coronary sinus tachycardia driving atrial fibrillation
No full textImages in cardiovascular medicineRotter, Martin; Sanders, Prashanthan; Takahashi, Yoshihide; Hsu, Li-Fern; Sacher, Frederic; Hocini, Mélèze; Jaïs, Pierre; Haïssaguerre, Miche
The Impact of Weight Fluctuation on Atrial Substrate and the Prevention of Atrial Remodelling With the Use of Anti-Fibrotics
Full text linkAtrial fibrillation (AF) is the commonest sustained arrhythmia in humans and is responsible for a significant socioeconomic burden. Affected individuals can suffer significant symptoms and are at risk of potentially life-threatening complications. Obesity is increasingly recognised as risk factor for the development of this arrhythmia. Weight fluctuation is common during attempted weight loss and has detrimental cardiovascular effects in human cohort studies, including patients with AF. However, the pathophysiological mechanisms by which this occurs are unclear. The first aim of this thesis is to characterise the electrophysiological effects of weight fluctuation using an obese ovine model. Previous studies have demonstrated that obesity promotes the development of atrial fibrosis as well as the upregulation of profibrotic factors in atrial tissue. The second major aim of this thesis is to investigate the effect of blockade of these profibrotic receptors on obesity-related atrial remodelling. Chapter 2 describes the use a fluctuating weight model in order to study the electrophysiological changes over time. Weight fluctuation was associated with progressive changes in atrial electrophysiology. This group demonstrated reduction in conduction velocity when compared to a lean control group, particularly following a second cycle of weight gain followed by weight loss. These changes were less severe when compared to an obese group. Additionally, the changes in conduction were more heterogeneous than in animals with persistent obesity. This resulted in an increased propensity to AF when compared with lean controls. Chapter 3 investigates the role of endothelin receptor blockade in the prevention of atrial substrate in obesity. Obesity was again induced in ovine subjects and two groups were compared. One was treated with the endothelin receptor antagonist (ERA) bosentan whilst the other acted as a control group. Animals treated with bosentan had attenuation of obesity-related conduction slowing. This was seen on both endocardial and epicardial surfaces. Importantly, there was no effect on either haemodynamics or refractory periods. AF inducibility was also reduced by ERA treatment. Examination of atrial demonstrated reduced fibrosis and downregulation of pro-fibrotic factors with ERA treatment. Importantly, this effect was independent of the TGF-β pathway. Chapter 4 examines the effect of the TGF-β receptor antagonist tranilast on the obese ovine atrium. A similar model of induced obesity was used to compare tranilast treatment with a control group. Animals receiving tranilast demonstrated attenuation of conduction slowing. Endo and epicardial mapping showed this slowing was heterogeneous across atrial sites, perhaps suggesting a predominantly local mechanism in the development of these electrophysiological changes.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The role of myocardial fibrosis and ventricular mechanical dyssynchrony in the pathogenesis and treatment of contractile myocardial dysfunction.
Full text linkStructural and functional abnormalities of the left ventricle and atrium are important prognostic factors in patients with cardiovascular disease. Dysfunction of the left ventricle in heart failure exposes the left atrium to elevated pressures during diastole, which result in adverse left atrial remodelling and impairment. Although the development of systolic left ventricular impairment has been linked with a number of causative factors, the pathophysiological cascade between these initiators of myocardial dysfunction and its overt manifestation has been incompletely characterised. Amongst the proposed intermediaries of systolic heart failure, recent attention has focussed on myocardial fibrosis and ventricular dyssynchrony. Myocardial fibrosis describes the extracellular deposition of collagen in response to an injurious process. This collagen deposition plays an important role in left ventricular remodelling, and may perpetuate myocardial dysfunction. Ventricular dyssynchrony refers to the incoordinate contraction of the ventricles: inter-ventricular dyssynchrony is the temporal uncoupling of left from right ventricular contraction, and intra-left ventricular dyssynchrony pertains to heterogeneity in the time to regional mechanical activation within the left ventricle. Ventricular dyssynchrony has also been implicated in the pathogenesis of systolic heart failure,
and its treatment by cardiac resynchronisation has been proven efficacious in selected patients with systolic left ventricular dysfunction. Despite emerging evidence implicating myocardial fibrosis and ventricular dyssynchrony in heart failure, their causal relationship with each other, and their relative importance in the pathogenesis of myocardial dysfunction have been poorly characterised. The aims of this thesis are to 1) characterise the role of myocardial fibrosis and ventricular dyssynchrony in the development of left ventricular and atrial
mechanical dysfunction, and 2) examine the importance of myocardial fibrosis and ventricular dyssynchrony in the response to therapy of patients with systolic heart failure using non-invasive imaging approaches. The first study presented in this thesis in Chapter 3 explores the relationship between left atrial mechanical and left ventricular function by evaluating the effects on left atrial mechanical function of eliminating left ventricular function through the temporary induction of ventricular fibrillation in patients undergoing routine defibrillation threshold testing following implantable cardioverter-defibrillator insertion. In this mechanistic study, the dependence of left atrial function on left ventricular function is demonstrated. This finding establishes the context for the subsequent research in this thesis on the effects of left ventricular function on the left atrium in idiopathic dilated cardiomyopathy and cardiac pacing. Chapter 4 presents research investigating the prevalence of myocardial fibrosis and ventricular dyssynchrony in patients with a first presentation of idiopathic dilated cardiomyopathy. The influence of these factors, amongst other recognised prognostic factors in heart failure, on recovery of left ventricular systolic function is
examined. The key finding of this chapter is that myocardial fibrosis and ventricular dyssynchrony are independent predictors of improvement in left ventricular systolic dysfunction amongst these patients. These results relate directly to the chief aims of this thesis. In Chapter 5, abnormalities in left atrial structure and function in patients with a first presentation of idiopathic dilated cardiomyopathy are explored. This research demonstrates that structural and functional abnormalities are prevalent early in the time course of this condition, but that these derangements are reversible following appropriate medical therapy. This chapter extends on the findings of the previous two chapters to illustrate how disease processes primarily affecting the left ventricle can impact upon the left atrium. Chapter 6 aims to further develop the evidence that left ventricular dyssynchrony promotes ongoing left ventricular dysfunction through the study of patients who had been enrolled in a randomised trial of right ventricular apical versus right ventricular outflow tract septal pacing for bradycardia. The major findings of this research are that right ventricular apical pacing is associated with greater ventricular dyssynchrony, poorer left ventricular function and worse adverse left ventricular remodelling than outflow tract septal pacing. Moreover, the adverse left atrial structural and functional effects of right ventricular apical pacing and ventricular
dyssynchrony are demonstrated. These results lend support to the theme that ventricular dyssynchrony, in this instance induced by pacing site, adversely influences left ventricular function, which in turn impacts in a deleterious manner on left atrial structure and function. In chapter 7, the final study conducted in this thesis, the intuitive question arising from the findings of chapter 6 is addressed, namely: if induction of ventricular dyssynchrony is deleterious, is its reversal therapeutic? This study randomised patients undergoing cardiac resynchronisation therapy for advanced heart failure to routine simultaneous bi-ventricular pacing, or echocardiographic optimisation of V-V
timing during bi-ventricular pacing, with the goal of further reduction in ventricular dyssynchrony. This study was unable to demonstrate a benefit of routine V-V optimisation in recipients of cardiac resynchronisation therapy despite achieving less left ventricular dyssynchrony. A trend towards improved functional status was observed, however. This thesis has led to an improved understanding of the mechanisms underlying the development and perpetuation of left ventricular and atrial dysfunction, and the determinants of their response to heart failure therapy. Work of this nature may allow the identification of novel diagnostic and therapeutic approaches to heart failure in the future.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Acute and chronic atrial remodeling in obstructive sleep apnoea : implications for atrial fibrillation.
Full text linkAtrial fibrillation (AF), the most common sustained arrhythmia, has been well studied; however, its underlying mechanisms and relationships to other disease processes have not been fully explored. Observational data from epidemiological studies have suggested a relationship between obstructive sleep apnoea (OSA) and AF. Recent clinical studies have implicated an adverse outcome to therapy in patients with AF and OSA. Despite several candidate mechanisms advanced, the acute and chronic changes to the atrial myocardium have not been fully characterised. This thesis evaluates symptomatic patients with AF presenting for
radiofrequency ablation of their arrhythmia. The acute and chronic electrophysiological and electroanatomical atrial substrate is characterised. Finally the effect on clinical outcomes of therapy directed at AF is evaluated with specific reference to the presence of OSA. Chapter 2 demonstrates the differences in the atrial substrate in paroxysmal and persistent AF. This study found persistent AF was associated with a reduction in electrogram voltage and greater signal fragmentation, with these two attributes being negatively associated. Chapter 3 examines patients presenting with symptomatic AF, previously not known to have sleep disordered breathing. OSA was associated with a greater symptomatic burden of AF as well as chronicity of the arrhythmia. In the presence of more severe OSA, there was a greater chance of failure of radiofrequency ablation in maintaining sinus rhythm. Chapter 4 characterises the underlying atrial substrate resulting in AF in patients with moderate to severe untreated OSA. OSA patients had larger atria, greater areas of low voltage and areas of electrical silence, suggesting loss of atrial myocardium. There were also markedly reduced conduction velocities, longer corrected sinus node recovery times and more conduction abnormalities characterised by complex electrograms. These findings provide important insights into the adverse remodeling that may allow AF to develop and persist in these patients, and promote the failure of ablation strategies. Chapter 5 examines nocturnal atrial electrophysiological alterations resulting from acute episodes of respiratory disturbance associated with hypopnoea and obstructive apnoea events the night after undergoing radiofrequency ablation for AF. Dynamic changes in effective refractory period (ERP), conduction times and conduction delay along linear catheters were documented. The changes appeared to be more marked for obstructive apnoeas than hypopnoeas. This study suggests a dynamic, pro-arrhythmic electrical substrate that could potentially lead to nocturnal triggering of AF and its maintenance. Finally, Chapter 6 describes an ex-vivo rabbit model, created to examine the acute effects of hypoxia (moderate and severe) and hypercapnia. Left atrial ERP, conduction time and conduction heterogeneity were studied using a customised microelectrode array. During hypoxia, there was a dose dependent increase in ERP with only partial resolution on restoration of baseline oxygen levels. With hypercapnia, there was a slower rise in ERP that did not appear to recover. Slowing of conduction was most noted in severe hypoxia, with only partial resolution in recovery. In hypercapnia, there was progressive
slowing of conduction into recovery. Conduction heterogeneity was also increased in the presence of hypoxia and hypercapnia. These findings further suggest complex alterations to the atrial electrophysiology in the presence of hypoxia and hypercapnia, with dynamic changes to in refractory periods, conduction times and heterogeneity. Together, a greater understanding of the acute and chronic effects of OSA on AF, and an appreciation of the failure of ablation strategies in the presence of this breathing disorder is attained. This paves the way for further studies on the mechanisms involved, and on the potential role for continuous positive airway pressure therapy (CPAP) in the management of patients with OSA and AF.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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