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
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.
Noncontact Biventricular Mapping And Intramural Ablation In A Chronic Ovine Model Of Septal Ventricular Tachycardia
Funder
National Health and Medical Research Council
Funding Amount
$519,279.00
Summary
Ventricular tachycardia (VT), an abnormal rhythm originating from the bottom portion of the heart is the major cause of sudden death in the community. Medications are not reliably effective. Expensive (costing about $40,000 every 5 years) implanted defibrillators are very effective in terminating VT, but frequently require painful shocks. Patients who require frequent treatment from their defibrillators are considered for mapping and ablation. About half of the patients with VT have the arrhythm ....Ventricular tachycardia (VT), an abnormal rhythm originating from the bottom portion of the heart is the major cause of sudden death in the community. Medications are not reliably effective. Expensive (costing about $40,000 every 5 years) implanted defibrillators are very effective in terminating VT, but frequently require painful shocks. Patients who require frequent treatment from their defibrillators are considered for mapping and ablation. About half of the patients with VT have the arrhythmia originating from the septum (heart muscle separating the two bottom portions of the heart). This area of the heart is difficult to map from an electrical point of view. A new type of mapping system called the Ensite 3000 system enables acquisition of 3,300 virtual electrical signals from within a heart chamber using an electrode array that does not have to be in direct contact with the heart muscle surface. Our evaluation of the Ensite system in one chamber of the heart has found it to be very good in identifying areas of abnormal electrical activity. It is possible that simultaneous mapping from both sides of the septum using Ensite might be useful in mapping VT originating from the septum. Destruction of the abnormal area, once identified, is generally done using a catheter, but is limited by its ability to destroy targets deep in the heart tissue. We have designed and developed a catheter that is equipped with a needle at its tip that can create deeper lesions. In this study we will be evaluating mapping using the Ensite electrodes in both ventricles in a chronic sheep model with VT originating from the septum. The Ensite mapping will be validated with detailed contact (conventional) mapping. The prototype catheter will be used to destroy the site of origin of VT, once identified. This study should enable more effective treatment of patients with VT and improve their quality of life.Read moreRead less
Characterisation Of Alterations In The Androgen Signalling Axis That Contribute To Treatment Failure In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,157.00
Summary
Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical mean ....Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical means (ie androgen ablation) is the only effective treatment option available. While androgen ablation is initially effective, treatment failure is common, resulting in a very poor overall survival rate. Evidence from our studies and others suggest that, the androgen receptor, which mediates the growth regulatory effects of androgens is often defective in prostate tumour cells. These altered or mutant receptors are activated inappropriately by other sex hormones such as estradiol and even agents used in the treatment of prostate cancer whereas the normal receptor is activated only by testicular androgens. This mechanism may explain why treatment fails in a subset of men with advanced prostate cancer. The major objective of our current studies is to define how these mutant androgen receptors cause treatment failure and facilitate prostate tumour growth. In addition, the current studies will evaluate a novel approach to treatment of prostate cancer which, based upon our preliminary results, has the potential to be effective even if alterations are present in the androgen receptor. The current studies therefore will provide a better understanding of factors controlling the growth of prostate tumours, and develop improved treatment approaches for advanced prostate cancer.Read moreRead less
Geldanamycin Derivatives: Novel Inhibitors Of Androgen Signalling For The Treatment Of Metastatic Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$316,320.00
Summary
Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as lymph nodes and bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical ....Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as lymph nodes and bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical means (ie androgen ablation) is the only effective treatment option available. However, androgen ablation is only palliative, and treatment failure is common, with less than 20% of patients surviving more than 5 years. Recent evidence suggests that the androgen receptor, which mediates the growth regulatory effects of androgens, such as testosterone, is often defective in prostate tumour cells. These altered or mutant receptors may be inappropriately activated and stimulate tumour growth which may explain why treatment fails in a subset of men with advanced prostate cancer. The major objective of our current proposal is to evaluate a novel approach for the treatment of prostate cancer which, based upon our preliminary results, has the potential to be effective even if alterations are present in the androgen receptor. Specifically, we will examine the effectiveness of derivatives of a natural product, the antibiotic geldanamycin, to inhibit prostate tumour growth. The current studies therefore have the potential to result in improved treatment approaches for advanced prostate cancer.Read moreRead less
Androgen Receptor Signalling And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$462,750.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to current forms of androgen ablation therapy. Inappropriate activation of androgen signalling by non-testicular androgens or other agents may stimulate tumour growth following androgen ablation. In this study, we aim to identify and characterise determinants of the specificity and sensitivity of activation of the androgen receptor, which is the primary mediator of androgen action. Current androgen ablation treatments for prostate cancer only target the availability of androgenic ligands. We propose that it is also necessary to target the androgen receptor itself, because it can be activated by ligands other than testicular androgens. Therefore, we will also evaluate a panel ofagents that target different aspects of the androgen signalling axis, combined with androgen ablation using a cyclical approach to prevent or delay disease progression.Read moreRead less