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.Read moreRead less
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.Read moreRead less
Atrial Electrical Remodeling Due To Chronic Stretch: Defining The Substrate For Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood ....Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood. There are several forms but the basic problem is leakage of blood from the left atrium into the right atrium .This also puts a strain on the heart and can cause heart failure. All 3 conditions are associated with a significantly increased risk of atrial fibrillation (AF). This abnormal fast irregular cardiac rhythm makes the pumping of the heart inefficient. People with AF may feel short of breath, tired, or develop palpitations. AF is an important cause of stroke and premature death and is the most common heart rhythm disturbance occurring in upto 10% of the over 70 age group. Even after repair of the leaky valve or atrial septal defect there is still a high risk of developing this rhythm. Purpose of the study: This study will try to understand why patients with these conditions are at risk of developing atrial fibrillation, and why this risk might persist after surgical correction when this is possible (mitral regurgitation and atrial septal defect). The study will utilise sophisticated new mapping techniques to gain original insights into the mechanism of this very common and as yet poorly understood heart rhythm disturbance. The study has the potential to determine the cause of atrial fibrillation in these patient groups and as such represent a quantum advance in our understanding of he mechanism of atrial fibrillation. It would be expected to form a foundation on which development of curative and preventative approaches may be based.Read moreRead less
Stretch Induced Pulmonary Vein Remodelling: Implications For The Initiation And Maintenance Of Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$569,823.00
Summary
Atrial fibrillation (AF) is the most common heart rhythm disorder to affect humans, occurring in 2% of adults. It is a chaotic rhythm disorder of the top chambers of the heart that results in frequent hospitalization for falls, chest pain, palpitations, heart failure and stroke. In addition, it is associated with an increased mortality. Evidence suggests an important role of the pulmonary veins (PV; veins draining blood from the lungs back to the heart) in the initiation and maintenance of AF. H ....Atrial fibrillation (AF) is the most common heart rhythm disorder to affect humans, occurring in 2% of adults. It is a chaotic rhythm disorder of the top chambers of the heart that results in frequent hospitalization for falls, chest pain, palpitations, heart failure and stroke. In addition, it is associated with an increased mortality. Evidence suggests an important role of the pulmonary veins (PV; veins draining blood from the lungs back to the heart) in the initiation and maintenance of AF. However, why these structures promote AF remains unknown. Several conditions predisposing to the development of AF are associated with atrial stretch (such as heart failure). These conditions have documented abnormalities within the atria but the changes that occur within the PVs are unknown. It has even been suggested that pulsatile stretch, as caused by blood flow, in the appropriately predisposed patient, may be enough to trigger AF. As such there has been an intensive search to identify the abnormalities that occur within the PVs. In patients with AF, the PVs demonstrate distinctive electrophysiological properties compared to those without AF. However, the effect of stretch, a common predisposing factor, on the electrophysiological properties of the PV is not known. Preventing electrical activity from the PVs interacting with the heart by ablation has provided a glimpse at our ability to cure AF. However, further improvements in our procedural technique, the ability to prevent the occurrence of this rhythm disorder, and the development of noninvasive strategies to cure AF, hinges on the better understanding of the mechanisms initiating and maintaining this condition. In particular, the electrophysiological changes within the PVs that predispose patients to the development of AF need to be investigated. This series of studies will evaluate the effect of acute and chronic stretch on the PVs in humans to determine why these structures promote AF.Read moreRead less
Effects Of N-3 Polyunsaturated Fatty Acids On Post Surgical Atrial Fibrillation: A Prospective Randomised Study
Funder
National Health and Medical Research Council
Funding Amount
$536,529.00
Summary
Consumption of fish and fish oil has been associated with protective effects for deaths from heart disease in many studies. The effects are consistent and quite strong and appear to be unrelated to blood cholesterol levels. The effects are more likely due to the possibility that fish oil, which contains n-3 fats, can suppress abnormal heart rhythms which can cause 'sudden cardiac death'. This has been shown in animal studies, and recently we have shown that they can also suppress abnormal heart ....Consumption of fish and fish oil has been associated with protective effects for deaths from heart disease in many studies. The effects are consistent and quite strong and appear to be unrelated to blood cholesterol levels. The effects are more likely due to the possibility that fish oil, which contains n-3 fats, can suppress abnormal heart rhythms which can cause 'sudden cardiac death'. This has been shown in animal studies, and recently we have shown that they can also suppress abnormal heart rhythms in humans. Patients undergoing coronary bypass surgery are particularly susceptible to abnormal heart rhythms in the upper chambers of the heart in the days immediately following surgery. While these abnormal rhythms are rarely life threatening, they can result in increased post-surgical complications and a longer hospital stay with associated increased costs to the health system. In this study we will determine whether providing high dose fish oil for 3 weeks immediately preceding coronary bypass surgery, will result in a reduction in the proportion of patients experiencing post-surgical abnormal heart rhythms. We will also examine the effects of n-3 fats on the incidence of other complications following bypass surgery and also the length of hospital stay. In addition, we will gather data which will provide insight into the mechanisms by which n-3 fatty acids produce their well documented benefits to patients with cardiovascular disease. The significance of this study is its ability to provide a protective strategy in heart disease in which the mechanism is understood, which is effective, and importantly, which will have the potential to provide savings to the health care system through a reduction in hospital stay.Read moreRead less
Signalling Pathways Activated By Atrial Dilatation And Their Relationship To Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$449,878.00
Summary
Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4 ....Atrial fibrillation (AF) is an abnormality of cardiac rhythm that affects a large percentage of the population, especially the ageing population, and causes increases in morbidity and mortality. AF is associated with structural heart disease, and especially with atrial dilatation. Current treatments are designed to treat symptoms rather than underlying causes, and most have undesirable side effects. It is our long term goal to study the involvement of the calcium-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and its immediate precursor phosphatidylinositol(4,5)bisphosphate (PIP2) in atrial fibrillation with a view to providing targets for therapy that are well tolerated. There is recent evidence that Ins(1,4,5)P3 and PIP2 can contribute to atrial fibrillation. Over the next 3 years we will study cellular signalling responses to acute and chronic dilatation of the atria and examine the relationship of these findings to clinical atrial fibrillation. We will identify the G protein and phospholipase C subtypes involved in responses to stretch and use tools developed in these studies in experiments with atrial fibrillation models.Read moreRead less
Efficacy Of Coronary Sinus Ablation For The Treatment Of Atrial Fibrillation: A Randomised Controlled Study.
Funder
National Health and Medical Research Council
Funding Amount
$377,917.00
Summary
Atrial fibrillation is the most common sustained cardiac arrhythmia in the population. Left atrial catheter ablation is rapidly becoming a drug free alternative treatment for drug-resistant atrial fibrillation. The proposed study will examine whether ablation at a unique anatomical site adjacent to the left atrium (the coronary sinus) will increase procedural success compared to the conventional approach.
Epicardial Mapping Of Persistent Atrial Fibrillation. Identifying AF Mechanisms In Different Atrial Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$654,341.00
Summary
Atrial fibrillation (AF) is a very common heart rhythm disturbance (arrhythmia) which carries with it an increased risk of having a stroke and a twofold risk of dying. At present, we still have only a limited understanding of the mechanism of AF when it becomes persistent. The aim of this study is to determine the critical mechanism of persistent AF in patients with different types of heart conditions. This knowledge is fundamental to the development of more successful curative approaches.