Efficacy And Mechanisms Of Exercise Training In Diastolic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$385,250.00
Summary
Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrom ....Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrome is most frequently due to ischemic or hypertensive heart disease, and most commonly occurs in the elderly. The optimal management of DHF is not well defined, although some drug trials are currently in progress. A number of studies have shown exercise training to improve functional capacity by 15-20% in typical heart failure. However, training has not so far been trialled in DHF. In this multicenter, multi-disciplinary study, we will study a training and control group to determine whether exercise capacity and DHF symptoms are responsive to exercise training. This work will teach us about the optimum exercise prescription, in terms of the duration and nature of training, as well as the safety and effectiveness of exercise training. By using a number of sensitive measurements of heart and vessel function (in which our group has special expertise), we will identify whether exercise training exerts its effect through improvement in vascular function and myocardial properties. If successful, the clinical implications of this study are that; 1. Exercise training will be adopted to improve functional capacity and symptoms of DHF 2. The merits of aerobic and strength training will be identified in DHF 3. Abnormal blood vessel function will be identified as a major and reversible contributor to DHFRead moreRead less
A Supervised Exercise Programme Following Hospitalisation For Heart Failure: Does It Add To Disease Management?
Funder
National Health and Medical Research Council
Funding Amount
$730,966.00
Summary
Congestive heart failure (CHF) is a common, disabling condition. Outcomes are improved by a post-hospital disease management programme (DMP) including education, support and followup from a team of nurses, doctors and other health professionals. This study looks at whether adding a supervised exercise programme to a DMP can reduce death rates and hospital stays, and improve physical function and depression in patients with a recent hospital stay for CHF.
Randomized Controlled Trial Of CPAP On Cardiac Function In Patients With Heart Failure And Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$140,906.00
Summary
Heart failure is a very common condition associated with disabling symptoms. The main symptoms are breathlessness, usually during sleep or upon exercise, and fatigue. Recent research has identified that sleep apnoea, a condition that occurs in about 50% of subjects with heart failure, is likely to be responsible for these symptoms. Moreover, treatment specifically aimed at sleep apnoea, namely continuous positive airway pressure (CPAP) delived via a small electric pump and nasal mask worn during ....Heart failure is a very common condition associated with disabling symptoms. The main symptoms are breathlessness, usually during sleep or upon exercise, and fatigue. Recent research has identified that sleep apnoea, a condition that occurs in about 50% of subjects with heart failure, is likely to be responsible for these symptoms. Moreover, treatment specifically aimed at sleep apnoea, namely continuous positive airway pressure (CPAP) delived via a small electric pump and nasal mask worn during sleep, may also improve the symptoms of heart failure. The study will involve subjects with stable heart failure on optimal drug treatment who have evidence of obstructive sleep apnea on an overnight sleep study. Obstructive sleep apnoea (OSA) is a condition in which the throat intermittently narrows or blocks during sleep (often associated with snoring) causing cessation of airflow or apnoeas. Associated with the apnoeas are vigorous efforts by the chest muscles to breathe (creating negative vacuum-like pressures within the chest - and around the heart) at a time of falling oxygen levels. Previous research has suggested that these obstructive apnoeas are detrimental to the heart. Volunteers will be randomized to either a control or a CPAP treated group for a three month period. The control and CPAP groups will receive intensive advice about good eating and sleeping habits as weight gain and sleep loss are factors known to aggravate heart failure and obstructive sleep apnoea. In addition to the lifestyle advice, the CPAP group will also be treated with nasal CPAP. The variables which we will measure include severity of sleep apnoea, exercise capacity, heart function at rest and symptoms. Symptoms will be measured using 4 very detailed and validated questionnaires.Read moreRead less
Heart muscle cells have little potential for regeneration, and after a heart attack or in response to chronic hypertension, they grow bigger, resulting in deterioration of function and heart failure. We have compelling evidence that the c-kit protein limits heart regeneration and function. We expect to demonstrate that c-kit inactivation can greatly improve heart regeneration and function after cardiac injury/stress. Our work will have major clinical significance for future heart failure treatme ....Heart muscle cells have little potential for regeneration, and after a heart attack or in response to chronic hypertension, they grow bigger, resulting in deterioration of function and heart failure. We have compelling evidence that the c-kit protein limits heart regeneration and function. We expect to demonstrate that c-kit inactivation can greatly improve heart regeneration and function after cardiac injury/stress. Our work will have major clinical significance for future heart failure treatment strategies.Read moreRead less
Importance Of The Transmural Distribution Of Viable Myocardium To Outcome Of Patients After Revascularization
Funder
National Health and Medical Research Council
Funding Amount
$268,800.00
Summary
After a heart attack, up to 50% of tissue showing reduced function can recover if blood supply is returned to normal with bypass surgery or balloon angioplasty. Because these procedures may be risky in cardiac patients, the investigators have used various imaging approaches including radionuclide and ultrasound techniques to predict regions where function will recover after intervention. The results of these tests may be discordant because they assess separate attributes of cardiac muscle, and s ....After a heart attack, up to 50% of tissue showing reduced function can recover if blood supply is returned to normal with bypass surgery or balloon angioplasty. Because these procedures may be risky in cardiac patients, the investigators have used various imaging approaches including radionuclide and ultrasound techniques to predict regions where function will recover after intervention. The results of these tests may be discordant because they assess separate attributes of cardiac muscle, and selection of patients for intervention on the basis of recovery of regional function ignores some other aspects that may be important. These include avoidance of heart enlargement, improvement of exercise capacity, and avoidance of heart rhythm disturbances and even other heart attacks. In this study, the investigators seek to define the importance of the proportion and site of live (viable) myocardium to the parameters listed above. A new magnetic resonance technique will be used to identify whether radionuclide and ultrasound techniques assess different parts of the heart wall. The relative importance of these sites will be identified by comparing the outcome of patients who have live tissue in the inner half, compared with the outer half of the heart wall. This study will involve 180 patients who will undergo testing with magnetic resonance and radionuclide imaging. A subgroup will undergo dobutamine echocardiography. Their responses over follow-up will be assessed by accurate evaluation of heart size, exercise response, heart rhythm abnormalities and clinical events.Read moreRead less
Acute Exercise And Digoxin Effects On Skeletal Muscle Na+,K+ATPase Regulation, K+ Homeostasis And Fatigue In Humans:
Funder
National Health and Medical Research Council
Funding Amount
$177,000.00
Summary
This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined ....This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined exercise leading to fatigue, does inhibit the sodium-potassium pump and whether recovery occurs within 3 hours after exercise. The sodium-potassium pump is comprised of several variations of very similar enzymes, known as isoforms, each under the control of a separate gene and having slightly different functions and regulation. We explore whether exercise causes the genes regulating these isoforms to be activated and whether this results in an increased isoform formation in the muscle cell. We use a drug commonly used in patients with heart failure, called digoxin, which blocks the action of the sodium-potassium pump. In rat muscles this reduces muscular performance, with earlier and more pronounced fatigue. We examine whether a similar detrimental effect occurs in muscles of exercising humans and measure the resultant effects on muscle sodium and potassium levels. Increased knowledge about the effects of a single exercise bout on muscle is important fundamental knowledge. The study will lead to new knowledge about sodium-potassium pump regulation in exercising humans and thus enhance our understanding of muscle fatigue and gene responses to exercise. Understanding exercise effects will assist in development of strategies to counter physical inactivity, which is a major burden on health in Australia. Improved understanding of the actions of digoxin will also benefit patients with heart failure, through modified drug use and development of more specific treatment.Read moreRead less
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
Sympathetic Nervous System Activation In Renal Failure. Its Contribution To Pathogenesis And Progression.
Funder
National Health and Medical Research Council
Funding Amount
$490,796.00
Summary
Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related t ....Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related toxins. However, renal transplant recipients with excellent graft function and no signs of uremia still exhibit increased sympathetic nerve firing. Most interestingly, bilateral nephrectomized patients have nerve firing rates comparable to that of normal control subjects without renal disease. These data suggest that the diseased kidneys exert excitatory effects on the sympathetic nervous system independent of correction of uremia. The proposed study aims to comprehensively investigate the pattern of sympathetic activation both centrally (microneurography) and regionally (radiotracer dilution methodology) in patients with chronic renal failure and end stage renal disease . The effect of the centrally acting sympatholytic drug rilmenidine on sympathetic activity in the setting of renal disease will be assessed. Patients with ESRD waitlisted for kidney transplantation will be studied before and after transplantation. Some of the transplant recipients will also have undergone uni- or bilateral nephrectomy before transplantation which will enable us to further explore the role of the diseased kidneys in sympathetic activation. The results of this study may prove to have significant implications for treatment and prevention of cardiovascular morbid events frequently associated with renal disease.Read moreRead less