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
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
State-dependence Of Drug Binding To HERG K+ Channels.
Funder
National Health and Medical Research Council
Funding Amount
$397,224.00
Summary
In recent years, it has become apparent that a wide range of prescription drugs can cause inadvertent inhibition of a potassium channel in the heart known as hERG, resulting in an increased risk of cardiac arrhythmias and death. This has prompted the withdrawal from the market of 9 drugs and the introduction of mandatory testing of all drugs for inhibition of hERG channels. In this proposal we seek a molecular explanation for the promiscuity of drug binding to hERG channels
Platelet And Endothelial Function In Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$105,825.00
Summary
Atrial fibrillation is the most common heart rhythm disturbance in the adult population and leads to substantial increased death and disability from stroke. In this research scheme, we will study the contribution of platelet (clot forming cells) and endothelial (lining of blood vessels) dysfunction in atrial fibrillation. The successful outcome of this project will lead to a better understanding of the underlying mechanisms of clot formation and may lead to a better target for future drugs.
Remodelling In Cardiac Hypertrophy: Implications For Arrhythmogenesis
Funder
National Health and Medical Research Council
Funding Amount
$48,361.00
Summary
High blood pressure (HBP) affects 1 in 3 adults. Cardiac hypertrophy (thickened heart muscles) is a common condition seen in HBP. This research seeks to study the underlying changes in electrical, structural and molecular properties of the heart that may contribute to the increased sudden death and atrial fibrillation (irregular heart rhythm) associated with both HBP and cardiac hypertrophy. The new understanding may identify new treatment targets to reduce these life-threatening conditions.
Analysis Of Atrial Electrical Remodelling In Patients With Paroxysmal And Persistent Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$127,516.00
Summary
I am a cardiologist undertaking further training in the management of electrical abnormalities of the heart. My research will focus on the mechanisms responsible for atrial fibrillation, the most common serious heart rhythm disorder. I intend to do this by examining the nature of the electrical activity in patients with atrial fibrillation and comparing this to electrical activity in patients without this disorder, who are undergoing treatment procedures for their electrical disorder.
Atrial fibrillation (AF) is the most common cause for an irregular heart beat. Catheter ablation is the only potential cure and involves passing wires via veins in the leg into the heart to deliver discrete small burns(ablation) around the pulmonary veins (PV), the major source for AF. Unfortunately 30-50% of patients have recurrent arrhythmia due to reestablishment of electrical connections. This multicentre internation trial examines whether more (maximal) ablation will improve the outcomes of ....Atrial fibrillation (AF) is the most common cause for an irregular heart beat. Catheter ablation is the only potential cure and involves passing wires via veins in the leg into the heart to deliver discrete small burns(ablation) around the pulmonary veins (PV), the major source for AF. Unfortunately 30-50% of patients have recurrent arrhythmia due to reestablishment of electrical connections. This multicentre internation trial examines whether more (maximal) ablation will improve the outcomes of the procedure.Read moreRead less
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.
Circumvenous Ablation For Treatment Of Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$341,844.00
Summary
Atrial fibrillation is the most common abnormal heart rhythm. It causes symptoms that may be disabling but also increases the risk of stroke and death. The lifetime risk of developing atrial fibrillation is 20-25%. Treatment with medications is often unsuccessful and is never curative. Recently a new minimally invasive procedure was developed that may cure some patients. The purpose of this clinical trial is to improve the curative technique to broaden the application of the new procedure.