Дисертації з теми "Atrial fibrillation substrate"

Atrial fibrillation is the most prevalent form of cardiac arrhythmia. Studies in animal modelshave provided important insights into arrhythmia mechanisms. However, to date, we do not dispose ofanimal models of spontaneous atrial arrhythmia.Thus, we aimed to develop a model of spontaneous atrial arrhythmia in rats and to assesspathophysiological mechanisms of these arrhythmias by using a multidisciplinary approach. We alsoaimed to assess the presence and the extent of inflammation and endothelial dysfunction, incriminatedin atrial fibrillation-related complications such as stroke, in atrial fibrillation patients.The animal study describes the first animal model of spontaneous atrial arrhythmias. We alsoprovide evidence that multiple mechanisms participate in arrhythmia occurrence in this model,particularly autonomic imbalance with relative vagal hyperactivity, left atrial endocardial fibrosis, anddecreased left atrial expression of the Pitx2 gene. In our clinical study, we found high levels ofvascular endothelial growth factor and von Willebrand factor in atrial fibrillation patients compared tosinus rhythm controls. These results suggest specific thromboembolic risk patterns according to theclinical form of arrhythmia and highlight a parallel evolution of atrial fibrillation and endothelialdysfunction. These results add new insights into the understanding of atrial arrhythmias. This new animalmodel could facilitate studies of pathophysiological mechanisms involved in atrial arrhythmias andallow assessment of efficacy and toxicity of therapeutic agents in a setting that faithfully reproducesthe clinical presentation of the arrhythmia

Atrial fibrillation (AF) is the most common cardiac arrhythmia that affects an estimated 33.5 million people worldwide. Despite its prevalence and economic burden, treatments remain relatively ineffective. Interventional treatments using catheter ablation have shown more success in cure rates than pharmacologic methods for AF. However, success rates diminish drastically in patients with more advanced forms of the disease. The focus of this research is to develop a mapping strategy to improve the success of ablation. To achieve this goal, I used a computational model of excitation in order to simulate atrial fibrillation and evaluate mapping strategies that could guide ablation. I first propose a substrate guided mapping strategy to allow patient-specific treatment rather than a one size fits all approach. Ablation guided by this method reduced AF episode durations compared to baseline durations and an equal amount of random ablation in computational simulations. Because the accuracy of electrogram mapping is dependent upon catheter-tissue contact, I then provide a method to identify the distance between the electrode recording sites and the tissue surface using only the electrogram signal. The algorithm was validated both in silico and in vivo. Finally, I develop a classification algorithm for the identification of activation patterns using simultaneous, multi-site electrode recordings to aid in the development of an appropriate ablation strategy during AF. These findings provide a framework for future mapping and ablation studies in humans and assist in the development of individualized ablation strategies for patients with higher disease burden.

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and a frequent cause of hospitalization. Moreover, it represents one of the most frequent complication following cardiac surgery with an incidence of around 30% and an important predictor of patient morbidity. The exact pathophysiological mechanisms responsible for the onset and perpetuation of AF are not completely understood. However, clinical and experimental insights on the factors causing AF have suggested that atrial fibrillation is a multi-factorial phenomenon. Atrial fibrillation is characterized by a highly complex and irregular electrical activation of the atrial tissue, which is the manifestation of diverse abnormalities (electrical, structural, metabolic, neurohormonal, and/or molecular alterations) in diverse pathological conditions. In particular, it has been shown that fibrosis, a phenomenon in which extracellular matrix (ECM) components, mainly fibrillar collagen, accumulate between cardiomyocytes, leads to the inhomogeneous atrial electrical conduction typical of fibrillation. Recent studies have suggested that the deregulation of gene expression may act as a molecular mechanism of arrhythmogenesis. In particular, miRNAs, a new class of non-coding RNAs have rapidly emerged as one of the key players in the gene expression regulatory network, so variations in their expression levels may constitute a pathway for the arrhythmia-induced atrial remodeling. The present study aims to investigate the structural and molecular features of atrial tissue, with particular attention to fibrosis, which may be involved in the formation of a pro-arrhythmic substrate. By using both histological and advanced microscopy techniques, intramural fibrotic content and 3D collagen network properties were determined in atrial samples, collected during cardiac surgery in patients who developed or not AF. The quantitative analysis indicated a general decrease of collagen content from the outer (the epicardium) to the inner (the endocardium) myocardial wall, in the overall patient population. However, AF patients presented higher fibrotic values compared to sinus rhythm (SR) patients in the deeper myocardial layers, thus supporting the hypothesis that an accumulation of fibrotic tissue within the myocardial wall may represent an important structural contributor in the pathophysiology of AF. In addition to a quantitative assessment, collagen properties such as fibers orientation (degree and anisotropy) and scale dimension, were determined by non-linear optical microscopy techniques. The analysis revealed that in SR patients collagen network showed a fine architecture characterized by thin fibrils with changing angles and directions compared to AF, where fibers tended to pack-up in larger bundles of defined directions. A quantitative analysis of the 3D collagen network features, throughout the atrial wall, revealed that fibers orientation and scale dimension changed along tissue depth in both SR and AF patients, with larger values of orientation and fiber changes in AF tissues. These results highlight the spatial rearrangement and thickening of the 3D collagen network in AF patients, suggesting its possible role in the maintenance of the arrhythmia. Numerous evidence indicated that also an altered regulation of gene expression may play an important role in the mechanisms of atrial remodeling which underlie AF. In this perspective, the expression pattern of some miRNAs known to target different genes involved in diverse mechanisms that underlie AF was evaluated. A panel of miRNAs (miR-1, miR-133a/b, miR-30c, miR-29a/b, miR-208a/b, miR-328, miR-499, miR-590 and miR-21), principally involved in the formation of a pro-arrhythmic substrate, was selected after an accurate review of the literature and analyzed by RT-qPCR, in AF patients versus SR individuals. To accurately determine the levels of analyzed miRNAs, their expression data are usually normalized relatively to endogenous and/or exogenous reference genes. To date, no general agreement between different normalization strategies has been found, in particular in cardiac tissue, for the study of AF. For these reasons, a preliminary study aiming to establish the best endogenous reference genes for miRNAs data normalization was performed. Specifically, different well-established analysis tools such as NormFinder, GeNorm, BestKeeper and ∆Ct method, were applied on five commonly used endogenous reference transcripts such as 5S, U6, SNORD48, SNORD44 and miR-16. The suitable reference gene obtained, SNORD48, was applied for miRNAs data normalization. Our findings revealed that miRNAs expression levels were different in AF compared to SR patients. MiR-208a and miR-208b displayed statistically significant differences between the two populations. To investigate possible relationships between miRNAs expression levels and the fibrotic content a correlation measurement was also performed. Our analysis revealed that miR-21 and miR-208b were close to a significant correlation with fibrosis. In conclusion, this work introduced new techniques and implemented new methods of analysis for the study of the substrate of AF. In particular, the results obtained with this multiscale approach, from structural to molecular level, exacerbated the role of fibrosis as a critical contributor in the formation of a pro-arrhythmic substrate. Nonetheless, further studies are needed for a better understanding of the ways in which structural, molecular and also cellular remodeling may alter the impulse propagation in the myocardium.

The understanding of the underlying mechanisms of the persistence of atrial fibrillation remains poor. Key to this is the relationship between structure - myocardial architecture, and function - electrical activity, and how these can be measured, interpreted and correlated clinically. We sought to address the hypothesis that the local electrogram morphology is determined by local atrial myocardial activation patterns, which are in turn determined by local atrial myocardial architecture. In addressing this hypothesis, we utilised improved techniques of atrial segmentation and detection of wall enhancements to more accurately delineate underlying de novo atrial myocardial fibrosis, with late-gadolinium enhanced cardiac magnetic resonance imaging (LGE- CMRI). Here, we demonstrated a predilection of native structural remodelling on the posterior left atrial wall. The electrophysiological changes underlying late-gadolinium enhancements were interrogated with high-density electroanatomic 3D mapping using a Kernel as a unit of measure, in the varying rhythms of AF, sinus and pacing, with drop in tissue voltages and conduction velocities in regions of fibrosis, but counter-intuitively, a higher extent of electrogram fractionation in healthy myocardium. We observed the rate and wavefront-activation dependency of voltage, emphasizing the importance of voltage maps being interpreted in the context of its rhythm. We have also described a novel technique of AF voltage mapping, with the metric of mean AF voltage sampled over 8 secs correlating well with LGE-CMRI defined fibrosis, and surprisingly better than that of sinus rhythm voltage suggesting that this metric may be more representative of the underlying atrial substrate. Lastly, reverse translational cell monolayer experiments in novel co-cultured neonatal ventricular rat myocytes and fibroblasts were carried out to corroborate clinical in vivo observations under the control of the basic science laboratory. These emphasized the contributions of the structural and functional changes to electrogram morphology (voltage and fractionation). The contact electrogram is the result of a complex dynamic functional electrophysiology, and its interactions with the underlying atrial myocardium. This increased understanding of structure and function (electroarchitecture) provides mechanistic insights essential if we are to progress beyond the current empiricism of catheter ablation strategies of persistent AF.

The mechanisms responsible for maintenance of AF remain poorly understood. This thesis examines the frequency domain characteristics of AF in order to gain further insights into this arrhythmia. Through a series of studies involving patients undergoing catheter ablation for atrial fibrillation, intra-cardiac electrograms of AF were collected and analysed using Fast Fourier Transform to derive frequency domain parameters of dominant frequency (DF) and organization index (OI). It was found that intravenous flecainide reduced DF of AF, but only an associated increase in OI was predictive of successful return to sinus rhythm. In another study of patients having catheter ablation for persistent AF, a higher OI post-ablation was found to be associated with medium-term freedom of AF, suggesting that OI may be a useful guide to determine the extent of radiofrequency ablation needed. The effects of vagal blockade with atropine were also studied and compared with that of catheter ablation using a stepwise strategy of isolating the pulmonary veins, linear ablation and complex fractionated electrogram ablation, without deliberately targeting ganglionated plexi. This showed that atropine reduced DF and increased OI of AF electrograms, while decreasing mean RR intervals, standard deviation of RR intervals and 5th percentile of RR intervals. The directional changes of all the above parameters mirrored that of catheter ablation, suggesting that vagal blockade and catheter ablation not deliberately aimed at autonomic tissue can have similar effects on the frequency spectrum of AF, probably mediated through modulation of the autonomic tone. The relationship of regional DF and electrogram complexity as assessed by automated measurement of complex fractionated electrogram – mean (CFE-mean) were also compared, pre and post-ablation of the left atrium. There appeared to be only a modest correlation between the two and this was further weakened following ablation, suggesting that these are possibly separate substrate entities.

Le nombre d’adultes porteurs d’une tétralogie de Fallot opérée dans l’enfance est en constante augmentation. Initialement, ces patients étaient considérés comme guéris. A l’âge adulte, ils présentent en fait des complications d’ordre rythmique, responsables de morts subites, et des complications d’ordre mécanique : dilatation du ventricule droit (VD) liée à l’insuffisance pulmonaire chronique, séquellaire de la première chirurgie de réparation de la cardiopathie. Les mécanismes de l’arythmie ainsi qu’une éventuelle interaction entre la dysfonction VD et la survenue de ces arythmies ne restent que partiellement élucidés. Dans ce travail, en couplant les données d’études cliniques et les données expérimentales issues d’un modèle animal (MA) mimant une tétralogie de Fallot réparée, nous avons montré que 1) l’échocardiographie ne pouvait pas se substituer à l’IRM pour la surveillance des patients avec tétralogie de Fallot réparée 2) la valvulation pulmonaire restait une intervention à risque de mortalité 3) une bioprothèse non stentée était une bonne solution pour effectuer cette valvulation 4) en cas de fuite tricuspidienne sévère lors de cette valvulation, une plastie était indispensable 5) plusieurs gènes participaient au remodelage ventriculaire droit (analyse génétique effectuée sur le MA) 6) le remodelage électrophysiologique du VD (MA) s’accompagnait de propriétés pro-arythmogènes. Les mécanismes de décompensation sont intriqués : un lien entre dysfonction VD et arythmie paraît bien établi. D’autres analyses électrophysiologiques sont en cours au niveau du ventricule gauche (MA), pour rechercher d’autres mécanismes pro-arythmogènes
The number of adults with a repaired tetralogy of Fallot is increasing. In the past, those patients were considered healed. Nonetheless, they present arrhythmogenic issues, with frequent sudden death, and mechanical complications: right ventricular dilation due to long lasting pulmonary valve regurgitation, secondary to surgical repair. The origin of arrhythmia and its interaction with right ventricular dysfunction is only partially understood. In this study, combining clinical with experimental data, we pointed out: 1) concerning the follow-up of this population, echocardiography is not a substitute to MRI 2) operative mortality of pulmonary valve replacement (PVR) still exists 3) a stentless bioprosthesis represents a valid solution for PVR 4) a valve repair is mandatory for severe tricuspid valve regurgitation at PVR 5) the genetic analysis carried out in an animal model of repaired tetralogy of Fallot, demonstrated the involvement of numerous genes in right ventricular remodeling 6) remodeling of the right ventricle in this animal model generates pro-arrhythmic substrate. Heart failure mechanisms in repaired tetralogy of Fallot are complex: a link between right ventricular dysfunction and arrhythmias is demonstrated. Further studies are needed to investigate other pro-arrhythmic mechanisms involving the left ventricle

Atrial Fibrillation is the most common heart rhythm disorder. However, our understanding of the underlying patho-physiological mechanisms of AF remains limited. Both hypertension and heart failure are known to play an important role as risk factors for AF. With the increase in the incidence and prevalence of both these conditions and the predicted atrial fibrillation epidemic, their underlying mechanistic associations require careful attention. This thesis focused on the evaluation of atrial remodeling in large animal models of these common substrates. Chapter 2 presents the detailed anatomical, histological and functional characterization of the cardiac changes in the ovine “one-kidney, one-clip” model of hypertension using state of the art cardiac magnetic resonance imaging. Chapter 3 presents the significant atrial electrical, structural and functional remodeling evident with short duration (mean of 7 weeks) of hypertension. Pivotal changes were seen in increased atrial interstitial fibrosis and the resultant conduction abnormalities. This highlighted the importance of early and aggressive therapy of hypertension which may prevent the development of an arrhythmogenic atrial substrate. Chapter 4 examines the time course of atrial remodeling during the development of hypertension over a period of 15 weeks. Anatomical and functional remodeling started early while structural changes in increased fibrosis occurred later in the remodeling process. The early changes were associated with increased atrial fibrillation inducibility while the late changes were associated with more prolonged induced atrial fibrillation episodes. This understanding of the time course of remodeling provided important insights, whereby a narrow window of opportunity exists for preventing more permanent structural changes that can sustain atrial fibrillation. This work also implicates the need to maintain good blood pressure levels in atrial fibrillation patients. In particular, recent evidence has shown that pre-hypertension is associated with increased incidence of atrial fibrillation. To date, experimental studies on atrial remodeling in heart failure had utilized one single animal model of rapid ventricular tachypacing induced heart failure. This model may not be representative of all types of cardiomyopathy in the heart failure syndrome since different underlying causes of heart failure have been shown to portend different prognostic value. Chapter 5 further evaluates atrial remodeling in heart failure using a recently characterized ovine model of non-reversible doxorubicin-induced non-ischemic cardiomyopathy. The main feature of atrial remodeling lies in the structural changes of atrial interstitial fibrosis with increased conduction heterogeneity which resulted in longer induced atrial fibrillation episodes. These findings suggest a consistent substrate for atrial fibrillation in different heart failure models indicating ‘remodeling of the same sort’. Chapter 6 presents the atrial effects of omega-3 fatty acids treatment in ovine heart failure. Omega-3 fatty acids prevented atrial enlargement, reduced atrial fibrosis and the related conduction abnormalities resulting in shorter atrial fibrillation episodes. Clinically, omega-3 fatty acids have been shown to provide additional albeit modest improvement in outcomes of heart failure patients above current evidence-based therapies. Therefore, omega-3 fatty acids may potentially provide a relatively affordable and non-toxic option to prevent adverse atrial remodeling and reduce atrial fibrillation burden in this subgroup of patients with heart failure.
Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2010

Atrial fibrillation and atrial flutter are the most common sustained arrhythmias, however their underlying mechanisms are yet to be fully characterised. This thesis evaluates the electrophysiological and electroanatomical substrate of the atria in patients with these arrhythmias. Experimental studies of atrial fibrillation have demonstrated effective refractory period shortening and conduction slowing as a result of atrial fibrillation giving rise to the concept that "atrial fibrillation begets atrial fibrillation". However, cardioversion to prevent electrical remodelling does not prevent progression of disease, suggesting a "second factor" drives this process. Chapters 2 and 3 evaluate the atrial substrate in patients with "lone" atrial fibrillation. These studies demonstrate such patients, remote from an arrhythmic event, have prolongation of atrial refractoriness, conduction slowing, impairment of sinus node function, site-specific conduction delay, lower voltage and a greater proportion of complex electrograms compared to reference patients. These abnormalities constitute the "second factor" critical to the development and progression of atrial fibrillation. Atrial flutter has a close inter-relationship with atrial fibrillation and these rhythms frequently co-exist. Atrial fibrillation often occurs in patients with heart disease known to demonstrate abnormal atrial substrate; whether similar substrate exists in patients with atrial flutter to account for the co-existence of both arrhythmias is unknown. Chapters 4 and 5 evaluate the atrial substrate in patients with atrial flutter, remote from arrhythmia, demonstrating structural abnormalities characterised by loss of myocardial voltage, conduction slowing and impaired sinus node function, without reduction in atrial refractoriness. These findings implicate a common substrate as the cause of the close inter-relationship between these arrhythmias. There is a frequent association between atrial arrhythmia and sinus node disease for which several mechanisms have been postulated. In addition, there is a size discrepancy between the anatomical sinus node and the much larger functional sinus node complex. little is known about normal sinus node function or the effects of remodelling due to arrhythmia. Chapter 6 characterises sinus node activation to determine the nature and extent of the functional sinus node complex in patients with and without chronic atrial flutter. The functional sinus node complex demonstrates dynamic shifts in activation with preferential pathways of conduction to atrial myocardium. Patients with atrial flutter demonstrate lesser voltage, longer conduction times along preferential pathways and a smaller functional sinus node complex. These findings provide insights into the function of the human sinus node in health and disease. Sites of complex fractionated atrial electrograms and highest dominant frequency are implicated in maintaining atrial fibrillation. Chapter 7 determines the minimum recording duration that accurately characterises electrogram complexity and activation frequency. An electrogram duration of 5 seconds is required to accurately identify these sites. Chapter 8 evaluates the relationship between sites of fractionation and high frequency activation during atrial fibrillation. Greater fractionation and higher dominant frequency are seen in persistent atrial fibrillation and left atria. Preferential areas of high dominant frequency are observed in paroxysmal but not persistent atrial fibrillation. Areas of complex fractionated atrial electrograms are found adjacent to sites of high dominant frequency.
Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2009

ABSTRACT Background: The epicardial adipose tissue is located between the myocardium and the visceral pericardium, lying directly above the myocardium without any fascia. Epicardial adipose tissue presents itself with histological features typical of the brown adipose tissue. It plays a cardioprotective role through thermoregulation, energy homeostasis and anti-inflammatory regulation. However, in pathological conditions, epicardial adipose tissue may have a pro-inflammatory effect. Less is known about the role played by epicardial adipose tissue in patients with a history of atrial fibrillation. Some studies suggest an association between increased epicardial adipose tissue (volume and thickness) and atrial fibrillation. Nonetheless, there is little data about histological characterisation of epicardial adipose tissue in patients with a history of atrial fibrillation. Aim of the study: To evaluate the quantitative (using echocardiography) and qualitative characteristics (intra-operatory biopsy for histological characterisation) of epicardial adipose tissue in relation to atrial fibrillation burden after coronary artery bypass graft. Patients and methods: Prospective single-centre study approved by the ethics committee of Verona and Rovigo in July 2018. Patients undergoing coronary artery bypass graft with preserved left ventricular ejection fraction were included, after giving informed consent. Patients with atrial fibrillation and immunosuppressive therapy history were excluded. All enrolled patients underwent a medical evaluation to collect clinical history, a transthoracic echocardiography to measure epicardial adipose tissue thickness and collection of a bioptic sample containing right appendage and epicardial adipose tissue during coronary artery bypass graft. After surgery post-surgical clinical course and telemetry were collected. Lastly, histological characterisation (PLIN1 and fibrosis) of the bioptic samples was performed. Results: 56 patients undergoing coronary artery bypass graft were enrolled between 10th September 2018 and 3rd September 2019 in Cardiology and Cardiac Surgery departments. The mean hospitalisation was 11,9 ± 6,9 days and the postsurgical hospitalisation was 7,9 ± 3,7 days. 44 (78,6%) patients were male and the median age was 68,45 ± 9,2 years. All patients were continuously monitored with telemetry from the day of cardiac surgery until discharge. No major complications occurred, only one death unrelated to the surgery. Out of the total number of patients, 22 (39%) had at least one episode of atrial fibrillation. In the population that developed atrial fibrillation there was a bigger atrial volume, a higher degree of diastolic disfunction (E/A rate), a thicker layer of epicardial adipose tissue and an older median age in comparison to the group that did not develop it. Epicardial adipose tissue measured using echocardiogram with a cut off of 4 mm was a predictor of atrial fibrillation with an OR of 1,49 [1,09-2,04], 73% of sensibility and 89% of specificity. Furthermore, from the histological analyses of biopsies, the patients with atrial fibrillation had a significantly higher percentage of fibrosis, while adipose infiltration was not significantly higher. Through univariate analysis, atrial volume (OR 1,05 CI 1,01-1,09, p 0,022), E/A rate (OR 0,04 CI 0,02-0,72 p 0,29), the percentage of fibrosis (OR 1,12 CI 1,00-1,25 p 0,045) and age (OR 1,17 CI 1,07-1,28 p 0,001) were predictors of atrial fibrillation as well as the thickness of the epicardial adipose tissue. Through multivariate analysis atrial volume (p 0,027), fibrosis (p 0,003) and age (p 0,039) were independent predictors of atrial fibrillation. Conclusion: Post cardiac surgical atrial fibrillation is frequent. Epicardial adipose tissue measured by echocardiogram, atrial volume, fibrosis and age are predictors of post cardiac surgical atrial fibrillation.

Atrial fibrillation is the most prevalent arrhythmia worldwide and remains one of the major causes of morbidity and mortality. Atrial fibrillation is an arrhythmia that has a various etiology and takes number of clinical forms. Due to the heterogenity of atrial fibrillation, it is necessary to individualize the optimal treatment strategy, ie conservative pharmacological therapy or interventional therapy as catheter ablation. Inncorrect indication of catheter ablation of atrial fibrillation leads to low success rate of the procedure and increases the risk of the procedure. The success rate of catheter ablation of atrial fibrillation depends on many clinical parameters, including the size and volume of the left atrium and the presence of pathological tissue in the atrial myocardium. In everyday practice, echocardiography (2D-echocardiography) is the most dominant method in estimation of the left atrial parameters, for it's simplicity, non- invasiveness, financial costs and the absence of ionizing radiation. Different methods for assesment of left atrial parameters are cardiac CT, cardiac magnetic resonance imaging and methods of 3-D echocardiography or 3-D angiography. The results of the present studies show that in patients with non-valvular atrial fibrillation who are indicated for catheter...

Background: Atrial Fibrillation (AF) is the most common atrial arrhythmia affecting Australia and the world, with patients with AF known to be at a 5times higher risk of stroke than that of the normal population. The substrates of AF are also known to significantly impact of this risk of stroke. Mitral stenosis (MS) is one of the leading causes of valvular AF in the developing world. Enlargement of the LA is one of the most common structural changes that occurs in MS and is known to lead to fibrosis and oxidative stress. These alterations can also cause atrial electrical remodelling leading to the development of AF. Patients with MS have been shown to have an increase in thrombogenic properties which include platelet reactivity, inflammation and endothelial dysfunction. The precise mechanisms which underlie this phenomenon of atrial thrombus formation in AF are still unknown, furthermore it is also unknown if the substrate (cause) of AF influences the thromboembolic profile in AF patients. This thesis aims to evaluate the peripheral and atrial thrombogenic profile of both AF and the major substrate MS and their differing disease states alter the thrombus potential. Methods: A total of 166 patients were collected for this study, 55 patients undergoing a radiofrequency ablation as a curative procedure for paroxysmal AF, at the Royal Adelaide Hospital, Adelaide, 59 patients with mitral stenosis (MS)undergoing a balloon valvuloplasty at the Christian Medical Centre in Vellore, India, and 52 with aged matched control subjects, diagnosed with left sided accessory pathway supraventricular tachycardia (SVT) undergoing a routine elective electrophysiological study. Blood samples were collected from the peripheral, RA and LA circulation, during each of these procedures, for further analysis through flow cytometry, platelet aggregation and ELISA tests. Echocardiographic studies were used for atrial structure measurements. Results: We found that within the AF population there is increase in thrombogenic markers within the heart compared to the peripheral circulation. More interestingly when comparing the MS and AF populations each of the different factors involved in thrombogenesis is altered differently, with AF having an increase in platelet reactivity and endothelial function (ADMA and ET-1) and inflammation through VCAM-1 and ICAM-1. However of inflammation through MPO, CD40L and IL-6 and structural remodelling (MMP-9 and TIMP-1) were more pronounced within the MS population. Conclusion: This study has shown that AF and the valvular AF substrate mitral stenosis (MS) have two distinctly different mechanisms leading to atrial thrombus formation. This shows that MS as a substrate for valvular AF impacts on atrial thrombus formation through remodelling and inflammation whereas non valvular AF affects endothelial function and tissue inflammation. This illustrates that the pathophysiology of each of the diseases states is different when comparing it to the normal haemostatic properties of the heart within a control (SVT) population to determine if these factors are in fact altered from the norm.
Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2014