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.
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
Modifying Factors And Phenotype Heterogeneity In Familial Hypertrophic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$394,405.00
Summary
Familial Hypertrophic Cardiomyopathy (FHC) is an inherited disorder characterised by abnormal thickening of heart muscle, resulting in clinical symptoms in affected individuals ranging from mild symptoms, to heart failure and sudden death. FHC is the commonest cause of sudden death in individuals aged less than 35 yrs in our community, and is caused by defects in genes (DNA) important in the heart's cellular structure and function. Understanding and identifying the molecular steps involved in ho ....Familial Hypertrophic Cardiomyopathy (FHC) is an inherited disorder characterised by abnormal thickening of heart muscle, resulting in clinical symptoms in affected individuals ranging from mild symptoms, to heart failure and sudden death. FHC is the commonest cause of sudden death in individuals aged less than 35 yrs in our community, and is caused by defects in genes (DNA) important in the heart's cellular structure and function. Understanding and identifying the molecular steps involved in how this defect in our DNA can lead to the clinical features of FHC, is the focus of the research described in this project. A common occurrence in families with FHC is the identification of two affected individuals within the same family (e.g. siblings) and who therefore have the same genetic defect, with variable clinical outcomes. For example, one sibling may have no symptoms and live a normal life, while his-her sibling, may develop severe symptoms, heart failure, and-or early sudden death. The reason for such diversity in clinical features, even amongst individuals with the same genetic defect, most likely reflects secondary modifying factors, e.g. genetic and-or environmental factors which modulate the expression of the primary FHC-causing gene defect. This project will focus on identifying and studying such modifying factors. One aspect of the project will focus on the identification of a genetic modifier which has been shown to exist in a genetically-engineered mouse model of FHC. A second aspect of the proposed research will focus on potential environmental factors, including pharmacological agents which may prevent disease progression, dietary factors, e.g. caffeine intake, and lifestyle factors , e.g. exercise. Through these studies, it is hoped that key molecules and important pathogenic mechanisms will be identified, leading to the development of potentially new therapies, to both treat, and ultimately prevent or cure this inherited cardiac disorder.Read moreRead less
Atrial fibrillation (AF) has reached epidemic proportions. It results in significant burden to the individual and community with palpitations, falls, strokes, and heart failure which have contributed to an exponential rise in health care usage and hospitalisation. This application will focus on the optimal management of AF with a focus not only on therapeutics but importantly on the prevention of the arrhythmia and minimising hospitalisation.
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypotheses that this pacemaker mechanism is also fundamental to mammalian heart pacemaking and conduction. Positive support for our hypotheses, as indicated by our findings on amphibian hearts and from pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less
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
Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
Type 2 diabetes is the most common endocrine disease in the world and up to 60% of diabetic patients have heart disease. Heart disease is the most expensive heath condition and biggest cause of death in Australia. Diabetic patients often accumulate fat (triglyceride) within their heart cells, leading to diabetic heart disease. The present study sought to determine if diabetic patients with increased fat within their heart cells have more scarring which eventually results heart muscle dysfunction ....Type 2 diabetes is the most common endocrine disease in the world and up to 60% of diabetic patients have heart disease. Heart disease is the most expensive heath condition and biggest cause of death in Australia. Diabetic patients often accumulate fat (triglyceride) within their heart cells, leading to diabetic heart disease. The present study sought to determine if diabetic patients with increased fat within their heart cells have more scarring which eventually results heart muscle dysfunction.Read moreRead less
Atrial Fibrillation And Hypertension: Reverse Cardiac Remodelling Post Renal Denervation
Funder
National Health and Medical Research Council
Funding Amount
$90,144.00
Summary
Patients with hypertension are at increased risk of heart rhythm disorders, yet little is known if treatment of high blood pressure will improve abnormal rhythm. Renal denervation is a new and effective treatment for severe hypertension; this study will assess the adverse changes in heart structure and function due to severe hypertension, and investigate whether renal denervation can ameliorate these changes on a structural and electrical level.