Effects And Mechanisms Of Direct Cardiac Compression In Interruption Of Myocardial Remodelling In Chronic Heart Failure.
Funder
National Health and Medical Research Council
Funding Amount
$392,250.00
Summary
Heart failure (HF) is a disease where the heart pumping function is insufficient to provide adequate blood supply to the rest of the body. It is a highly debilitating disease affecting nearly 10 million people worldwide and has a <50% one-year survival in severe cases. Despite significant advances in pharmacotherapy, heart transplant is the only alternative for severe HF but is restricted by lack of donor organs to only ~ 5% of those requiring it. Research has shown that progression of HF is ....Heart failure (HF) is a disease where the heart pumping function is insufficient to provide adequate blood supply to the rest of the body. It is a highly debilitating disease affecting nearly 10 million people worldwide and has a <50% one-year survival in severe cases. Despite significant advances in pharmacotherapy, heart transplant is the only alternative for severe HF but is restricted by lack of donor organs to only ~ 5% of those requiring it. Research has shown that progression of HF is related to many subsequent changes after an initial insult. In addition to pumping failure, HF is associated with deranged compensatory responses such as neurohumoral over-activation, heart chamber enlargement, loss of functional cells, increase of inflammatory mediators and changes in cardiac skeleton (extracellular matrix). The changes in the heart are collectively known as remodelling. Mechanical heart assist is now considered a potential destination therapy for severe HF, superior to pharmacotherapy alone. Improvement of cardiac pumping function and even successful weaning from devices has been reported, along with observations of reverse remodelling. The success of this approach has been limited however, particularly with HF due to coronary disease, the most prevalent form. We developed a novel HeartPatch mechanical assist device to compress the heart from its outer surface. It gives support to both main chambers and avoids blood contact, a feature of currently available devices associated with complications such as blood clotting and infection. Our device has proved effective in animals with acute HF and even with cardiac arrest. We propose to study the effects of our device on the process of remodelling in HF with coronary disease in a controlled manner. The project will enhance understanding of the mechanisms involved in reverse remodelling and further the development of a device which may potentially benefit many severe HF patients.Read moreRead less
Development Of Non-surgical Approach To Treating Tricuspid Regurgitation
Funder
National Health and Medical Research Council
Funding Amount
$266,427.00
Summary
Heart failure is a common problem in which the heart enlarges and contracts poorly. In association with enlargement of the heart, the heart valves also begin to fail causing further worsening of quality and length of life. Failure of the tricuspid valve occurs in upto 87% of patients with heart failure and presently the only treatment option is high risk heart surgery. We are developing a way of dealing with tricuspid valve failure that does not require cardiac surgery.
Function Of The S100A1 Ca2+-binding Protein Under Physiological And Pathological Conditions
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
The S100A1 protein is one of the most abundant proteins in human heart muscle cells. It binds calcium ions and may play a role in the regulation of heart function. S100A1 levels are reduced in human heart failure, but it is unclear whether this reduction contributes to worsening of the disease. To study this, we have generated a genetically modified mouse strain that cannot make the S100A1 protein. We will use these mice to study how important the protein is for heart function under normal condi ....The S100A1 protein is one of the most abundant proteins in human heart muscle cells. It binds calcium ions and may play a role in the regulation of heart function. S100A1 levels are reduced in human heart failure, but it is unclear whether this reduction contributes to worsening of the disease. To study this, we have generated a genetically modified mouse strain that cannot make the S100A1 protein. We will use these mice to study how important the protein is for heart function under normal conditions, and how it contributes to the development of heart failure. Preliminary data indicate that adult mice with reduced S100A1 protein levels develop a form of heart disease that significantly reduces the efficiency of the pump function of the heart.Read moreRead less
Differences Between Physiological And Pathological Cardiac Hypertrophy Offer New Strategies For Treating Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$335,473.00
Summary
The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Spec ....The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Specifically my project hopes to identify the genes and proteins responsible for the differences. I have already identified one such gene and I now plan to manipulate this gene by overexpressing it in animals (transgenic mice) with heart failure. I predict that overexpression of this gene will improve heart function in models of heart failure. If the hypothesis is correct, activating genes that are activated in the athlete's heart maybe a potential tool for improving heart function, quality of life and life span in patients with heart failure.Read moreRead less
Cardiac-specific Therapy Targeting Hypertrophy And Apoptotis
Funder
National Health and Medical Research Council
Funding Amount
$542,683.00
Summary
We have discovered that certain pathological responses in the heart are mediated by an unusual type of signalling protein. The aim of the proposed studies is to determine whether this unusual signalling mechanism can provide a good target for development of new therapeutic approaches to prevent or treat heart failure.
Regulation Of Heart Development And Regeneration By DNA Methylation.
Funder
National Health and Medical Research Council
Funding Amount
$552,709.00
Summary
The adult mammalian heart has an extremely limited capacity for regeneration following a heart attack, which is in stark contrast to the robust regenerative capacity of the newborn heart. How and why mammals lose their ability to regenerate heart tissue after birth is not well understood. We propose a new approach to unravel the complex mechanisms that control gene expression during heart development in rodents and humans, which could provide new therapeutic avenues for heart regeneration.
Novel Multi-Modality Assessment Of Arrhythmic Risk And Disease Progression In Repaired Tetralogy Of Fallot Undergoing Redo-Pulmonary Valve Surgery Using 4D Cardiac MRI Flow And High Density 3D Electro-Anatomical Mapping.
Funder
National Health and Medical Research Council
Funding Amount
$110,703.00
Summary
Sudden death from arrhythmia is the most common cause of death in adults with tetralogy of Fallot, a type of congenital heart disease. It has been shown that dangerous arrhythmias can be induced in almost half of these patients when severe pulmonary valve disease is present. Our study will evaluate the potential for arrhythmias both before and after pulmonary valve surgery, using MRI and electrophysiological testing, to determine if these patients require defibrillators.