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  • Funded Activity

    Utility Of Direct Endocardial Visualisation To Characterise Scar Morphology And Ablation Lesion Formation

    Funder
    National Health and Medical Research Council
    Funding Amount
    $421,285.00
    Summary
    Endocardial visualisation is a new technique in which a catheter is used to look at the internal surface of the heart without the need for surgery. We will use the visualisation catheter to find a better way of placing small burns within the heart to stop atrial fibrillation (one of the most common heart diseases). We will also use the visualisation catheter to find a better way of locating the scarred areas of the heart responsible for ventricular tachycardia (another common heart disease).
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    Funded Activity

    Improving Outcomes In Patients With Life-threatening Ventricular Arrhythmias

    Funder
    National Health and Medical Research Council
    Funding Amount
    $606,009.00
    Summary
    This grant focuses on improving outcomes in patients with life-threatening ventricular arrhythmias (VAs). The AUGMENT-VA trial compares standard techniques for energy delivery during cardiac arrest with ‘manual pressure augmentation’, a novel technique which may improve energy delivery to the heart & restore normal rhythm sooner. The SUBSTRATE-VA study looks at the role of invasive mapping of the heart for unexplained VAs to identify subtle abnormalities that could be targeted for treatment.
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    Funded Activity

    Anatomical Template Mapping System

    Funder
    National Health and Medical Research Council
    Funding Amount
    $103,150.00
    Summary
    Improved electrophysiological mapping techniques have enhanced understanding of arrhythmia mechanisms and the development of curative ablation strategies. Advanced mapping systems utilize online visualization of catheters, 3D geometry, and annotation of ablation sites. To date, all commercially available systems rely on proprietary equipment to locate catheter positions and reconstruct chamber shape from multiple site recordings. Thus, cost is prohibitive, limiting widespread availability. An al .... Improved electrophysiological mapping techniques have enhanced understanding of arrhythmia mechanisms and the development of curative ablation strategies. Advanced mapping systems utilize online visualization of catheters, 3D geometry, and annotation of ablation sites. To date, all commercially available systems rely on proprietary equipment to locate catheter positions and reconstruct chamber shape from multiple site recordings. Thus, cost is prohibitive, limiting widespread availability. An alternative approach has emerged with the use of CT-MRI imaging and analysis. Novel techniques extract images of the endocardial surface from CT-MRI for use in electrophysiological mapping. This surface can be used as the chamber geometry instead of reconstruction based on expensive technology measuring spatial coordinates of the catheter tip inside heart. The proposed Anatomical Template Mapping System (ATMS) will generate maps of electrophysiological parameters derived from catheter recordings without the need for proprietary equipment. The physician will direct the virtual catheter position onto the 3D model of the chamber, obviating the need for equipment to map the spatial distribution of the catheters. The major advantage is that, without the need for specialized equipment, this method of mapping is substantially cheaper and can be used with any conventional electrophysiological mapping systems. Furthermore, it will provide the most important feature of the advanced mapping systems - an understanding of the arrhythmia mechanism.
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    Funded Activity

    Substrate Mapping And Ablation Of Ventricular Tachycardia

    Funder
    National Health and Medical Research Council
    Funding Amount
    $444,129.00
    Summary
    Sudden death is a tragic occurrence and can afflict Australians of all ages, racial and ethnic backgrounds. This research will aim to understand abnormalities in the heart muscle that cause dangerous heart rhythm abnormalities, which is the most common cause of sudden death. We will study ways to improve the technology of keyhole cardiac procedures so that it can be used to prevent these arrhythmias from occurring in the first place, and in improving the chance of long-term successful cure.
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    Funded Activity

    The Role Of Mechanoelectric Feedback In Cardiac Arrhythmogenesis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $307,550.00
    Summary
    Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. .... Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. In fact, the electrical activity of the heart is influenced strongly by the degree and timing of stretch to which the heart muscle is subjected, a process called Mechano-electric feedback. Since it can be demonstrated in isolated tissues, mechano-electric feedback must be an intrinsic property of the heart muscle. It has been shown in isolated heart preparations that passive stretch produces electrical disturbances in the normal action potential shape and propagation and that these electrical disturbances can be powerful enough to generate severe arrhythmias. There are paralells in human diseases. For example, atrial arrhythmias are common in older people, and it seems that these may be due to chronic stretch of the atria, as a consequence of high blood pressure. In addition, in those patients recovering from a heart attack, it seems likely that the damaged part of the heart muscle subjects the surrounding tissue to unusual mechanical stresses, and may trigger arrhythmias. This project aims to investigate the mechanisms underlying this mechano-electric feedback, in an attempt to understand some types of arrhythmias. Using molecular biology techniques, we will look at the gene expression of a novel type of stretch-activated potassium channel in both healthy and diseased animal hearts, with the aim of seeing if changes in the level of expression of these channels is correlated with changes in the response of the heart to stretch.
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    Funded Activity

    Structural And Functional Determinants Of Spatiotemporal Periodicity In Cardiac Impulse Propagation

    Funder
    National Health and Medical Research Council
    Funding Amount
    $211,320.00
    Summary
    Abnormal heart rhythms (cardiac arrhythmias) are responsible for much morbidity and excess mortality in Australia. Although many abnormalities leading to an abnormal heart rhythm may be successfully treated by medications or minimally invasive operative procedures there are several important ones which are not. These include the most common significant cause of an abnormal heart rhythm, atrial fibrillation, and the arrhythmias responsible for approximately half of sudden deaths, ventricular tach .... Abnormal heart rhythms (cardiac arrhythmias) are responsible for much morbidity and excess mortality in Australia. Although many abnormalities leading to an abnormal heart rhythm may be successfully treated by medications or minimally invasive operative procedures there are several important ones which are not. These include the most common significant cause of an abnormal heart rhythm, atrial fibrillation, and the arrhythmias responsible for approximately half of sudden deaths, ventricular tachycardia and ventricular fibrillation. Atrial fibrillation is a leading cause of stroke. Sudden death is associated with aging and is an increasing problem because of the rising mean age of the population. Recent negative attention on the side effects of medications used for the treatment of cardiac arrhythmias has appropriately increased interest in curative approaches requiring no onging medications. These procedures usually rely on mapping electrical activity in the heart and interrupting abnormal electrical pathways using radiofrequency electrical current. The procedures are unsuccessful when existing techniques fail to identify the underlying mechanism responsible for the abnormal heart rhythm or when the source of the abnormal beating cannot be localised within the heart. In this project we investigate the fundamental basis for a new approach to these problems. By examining the variability of the beat rate and the variability of the beat rate at different points within the heart we may be able to identify arrhythmia mechanisms and localise arrhythmia sources. In this project we will examine in groups of cells the structures and types of electrical circuits which give rise to certain types of beat-to-beat variability in the heart. This information will be essential for the interpretation of information obtained in later human studies and the subsequent development of new curative procedures for these problems.
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    Funded Activity

    Unique Isoform-specific Regulation Of Cardiac Ryanodine Receptors By Calcium Store Proteins

    Funder
    National Health and Medical Research Council
    Funding Amount
    $421,160.00
    Summary
    The importance of proteins that regulate calcium stores of heart muscle is graphically illustrated by massive changes in cell structure and function, which lead to ventricular fibrillation and fatality when the proteins are disrupted. We recently made the remarkable discovery that the proteins have a unique action in the heart which enhances cardiac contraction. We will discover the interaction sites between the proteins and will define novel therapeutic targets for heart failure.
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    Funded Activity

    Microwave And Laser Energies For Percutaneous Cardiac Ablation For The Cure Of Arhythmias

    Funder
    National Health and Medical Research Council
    Funding Amount
    $331,527.00
    Summary
    The commonest beating disorder of the heart is atrial fibrillation (AF). Whilst it can occur at any age it is more common in the elderly with 12% Australians over 70 y.o having it. AF is the cause of a third of all strokes and increases the risk of dying from any heart disease. Ventricular tachycardia (VT) is the commonest cause of death in the year after a heart attack. Currently these beating disorders are in most cases incurable and respond poorly to medications. We have developed an operatio .... The commonest beating disorder of the heart is atrial fibrillation (AF). Whilst it can occur at any age it is more common in the elderly with 12% Australians over 70 y.o having it. AF is the cause of a third of all strokes and increases the risk of dying from any heart disease. Ventricular tachycardia (VT) is the commonest cause of death in the year after a heart attack. Currently these beating disorders are in most cases incurable and respond poorly to medications. We have developed an operation for AF which is done by open heart surgery. It has been successful at curing some patients who suffer from AF and uses radiofrequency energy. The difficulty of radiofrequency energy is that it is not suitable in a large number of cases for this operation. We are developing Laser and Microwave catheters as alternatives to RF so that the success of the operation can be improved. These new microwave and laser catheters are being designed and tested to be used primarily in a minimally invasive procedure. They would be inserted via the veins with the patient under sedation. This would allow patients to go home sooner and have a recovery period of only a few days. As well as their application in the top chamber of the heart (atrium) for AF, these new energies will be adapted for minimally invasive operations in the ventricle (lower chamber) of the heart for the treatment of ventricular tachycardia. By developing a technique such as this, cure of AFand VT will be available to many more people, helping reduce the strokes, heart failure and premature deaths from these two heart conditions.
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    Funded Activity

    Structural And Functional Consequences Of Left Ventricular Hypertrophy Regression.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $293,036.00
    Summary
    Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and s .... Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and society in general. We propose to develop a mouse model of an inherited form of LVH that is caused by gene mutations in heart muscle proteins. This model will enable us to study in detail the disease processes that cause LVH and the effects of reversing LVH. This information will be invaluable for determining the best ways of treating patients with LVH.
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    Funded Activity

    Value Of Central Blood Pressure For GUIDing ManagEment Of Hypertension (BP GUIDE Study)

    Funder
    National Health and Medical Research Council
    Funding Amount
    $339,553.00
    Summary
    A pressure pulse may be felt at the wrist with every heart beat. New technology allows the analysis of this pulse and measurement of blood pressure (BP) at the heart (central BP) . This information may help doctors improve the decision making process regarding a patient's risk related to BP as well as the effect of drug treatment. The study aims to test this theory. It is expected that the new technology will improve the way people with high BP are identified and treated.
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