INTRODUCTION

The Department of Cardiovascular Medicine provides clinical services in the prevention and treatment of all forms of adult cardiac disease. Clinical activities of the department range from ambulatory clinics to reduce the likelihood of developing coronary disease, to the management of severe heart failure. The clinical activities are all closely integrated with the departmental research program undertaking both fundamental and applied research. This close integration allows research advances to be quickly introduced into clinical practice as well as facilitating the development of relevant research in areas of clinical need.

Research within the department is conducted by full time Alfred staff, staff who have joint appointments between the Alfred hospital and the Baker Heart Research Institute as well as full time researchers from the institute who conduct their clinical research within the department. Research within the department is funded from a number of sources including NHMRC program, project and special initiative grants. There is an additional funding from the National Heart Foundation as well as other charitable and commercial sources. In addition to the provision of training in clinical cardiology the department has a number of clinical PhD students who are able to complement their clinical cardiology training with research experience.

Two such former students, Dr James Shaw and Dr Andrew Taylor have rejoined the department in recent years in a consultant capacity having furthered their research through overseas experience. The continued recruitment of clinical staff with research experience and aspirations is essential to maintain an innovative and evolving research activity. This is also assisted by the presence of overseas trained cardiologists undertaking a period of research within the department. Other initiatives which will further enhance cardiovascular research include the relocation of the Australian Centre for Blood Diseases to the AMREP campus and joint research initiatives are already underway.

The accompanying report describes some of the research conducted within the department as well as detailing other notable achievements.

ALFRED BAKER GENE BANK

The Alfred Baker Gene Bank was initiated some years ago by Professor Garry Jennings, Associate Professor Christopher Reid and Professor Anthony Dart.

The objective was to enable the collection of genetic material from a range of cardiovascular patients along with relevant clinical information. The facility was managed for several years by Dr Carolyn Williams who has now left to undertake a genetic study funded by the WHO. During this time the number of samples has risen substantially to more than 4440 and routine collection is now occurring both in the coronary care unit, outpatient clinics and the cardiac catheter labs. The research value from such an activity is increased in proportion to the number of samples collected and this collection is well on target to achieve its initial goal. Already to date several studies have been published which were conducted either in or through the Gene Bank and several more are currently underway. A notable example is a study from Prof Kaye 'Relating genetic variation in the beta adrenoceptor to response to treatment in patients with Heart Failure". Other studies include 'The effect of variation in the MTHR gene on homocysteine responses to folate administration" as well as a number of studies on the matrix metalloprotinases as detailed elsewhere in this report.

CLINICAL TRIALS

International Collaborative trials.
Chief Investigator: Professor Anthony Dart
Research Co-Ordinators: Sally Kay and Kaye Carter

Recently Completed Trials
ACTION

This clinical end point study evaluated the effect of treatment with a calcium channel blocker (Adalat Oros) in patients with stable coronary disease. Treatment with the calcium channel blocker did not affect the incidence of major cardiovascular events but was associated with less need for procedures.

PROVE IT
This study was also conducted in patients with coronary disease and evaluated different degrees of lipid lowering as well as long term antimicrobial treatment. Results indicated an improved outcome with lower cholesterol levels but no effect of antimicrobial treatment on cardiac disease.

TNT
This study compared two doses of the same lipid lowering drug in patients with coronary disease. It also found that patients with the lower cholesterol (LDL < 2.0 mmol/L) had few events.

MERCURY
This study evaluated the lipid-altering efficacy and safety of Ezetimibe/Simvastatin combination tablet in patients with elevated cholesterol.

Current Trials
ILLUMINATE

In this recently initiated trial the effects of a new drug that increase HDL ("good") cholesterol will be tested in patients with coronary disease.

SECONDARY PREVENTION – THE COACH PROGRAM

(Caroline Calkin - Cardiac Coach)

The COACH Program is a disease management program for patients with coronary heart disease whereby a cardiac "coach" trains patients to aggressively pursue the National Heart Foundation of Australia's target levels for their particular coronary risk factors, while working in partnership with the patient's own doctor(s). The program was initially developed and evaluated in a clinical trial conducted in several metropolitan hospitals including The Alfred. The coach recruits patients prior to their discharge from hospital and then provides regular over the phone coaching session and mail outs to patients after discharge.

The program was established at The Alfred in December 2003, under the supervision of Professor Dart. 334 patients were recruited over 2003/2004. Analysis of patients coached for at least six months at The Alfred showed a substantial improvement in the proportion of patients reaching their risk factor targets. At six months, approximately three-quarters of patients achieved a total cholesterol of less than 4.5 mmol/L and approximately two thirds of patients achieved the blood pressure targets. Whilst improvements in the proportion of patients achieving the targets for body mass index and waist circumference were made, weight management remains a very significant problem. Nearly all patients were on antiplatelet agent/s and a statin, about two thirds of patients were taking a β blocker and about three-quarters were taking an angiotensin II receptor antagonist or angiotensin converting enzyme inhibitor.

A four year follow up of patients involved in an earlier multicentre randomised controlled trial of coaching has shown a 20% reduction in the total number of bed days in hospital in patients who had been coached, compared to patients receiving usual care.

PERIPHERAL INTERVENTIONAL PROGRAM

(Dr James Shaw)

The Alfred Minimally Invasive Vascular Centre (AMVC) was established in March 2004 as a collaboration between the dept of Cardiology and Radiology. It provides both the latest in medical and percutaneous treatment of non-coronary vascular disease as well as the opportunity to carry out research projects in this growing area. At this stage 2 projects have received ethics approval and recruitment has begun. The first involves looking at predictors of blood pressure responses in patients undergoing renal artery revascularisation for difficult to control hypertension. To date 12 patients have been recruited with the plan to recruit a total of 50 patients by June 2006. The second project involves administering HDL (the good cholesterol) to patients with known narrowing in their leg arteries. Plaque is then removed with an atherectomy catheter and examined microscopically to detect early changes resulting from the HDL administration. Patient recruitment is expected to start in April.

HEART FAILURE AND HEART TRANSPLANT RESEARCH

(Prof David Kaye)

Management of patients with end-stage Congestive Heart Failure (CHF) is a major focus of the Alfred Hospital Cardiology Department. In association with partners at the Baker Heart Research Institute and Monash Medical School, research into the pathophysiology and treatment of CHF is a major AMREP activity. The skills of various team members has allowed the development of an internationally renowned group whose skills range from the application of genetic, molecular and cellular techniques through studies in transgenic and large animal models of CHF to 'first in man' clinical trials. Amongst several notable successes this year, the Alfred HF team were the first in the world to implant a catheter-based non-surgical method for the treatment of mitral valve regurgitation (developed by Dr David Kaye and his Baker collaborator Dr John Power). The group also continued to lead the clinical trial of the Ventracor artificial heart device. In the area of heart transplantation, the Alfred team (under the guidance of Dr Meroula Richardson) participated in a landmark international trial of sirolimus, a new immunosuppressive drug. In addition to research into new treatments, Dr Andrew Taylor has applied MRI technology to imaging the moving heart 'Cardiac MRI'. This innovative diagnostic tools provides unique information, which has radically improved the treatment of CHF patients at the Alfred.

LARGE ARTERIES

(A/Prof Bronwyn Kingwell)

Large artery stiffness as a risk marker and therapeutic target; structural and genetic aspects
Large artery stiffness is a newly identified independent risk marker for cardiovascular disease. Through an integrated series of human, animal and cell culture studies we are investigating the mechanisms by which large artery stiffness increases cardiovascular risk. These studies are directed towards improving cardiovascular risk prediction and reducing risk through therapeutic targeting of large artery stiffness

Large artery stiffening causes pulse pressure elevation and both parameters are related to cardiovascular mortality independently of other major risk factors. The mechanism underlying this relationship could be due to similar disease progression in the coronaries and aorta. Alternatively, intrinsically stiff large vessels may promote atherosclerosis throughout the circulation through pulse pressure elevation and subsequent mechanical fatigue and endothelial disruption.

Our work has identified specific structural and genetic determinants of large artery stiffness in relation to cardiovascular risk prediction. We have identified large artery stiffness as an important ischaemic mechanism and have shown that ACE inhibition is an appropriate therapy to improve symptoms and reduce large artery stiffness in patients with peripheral arterial disease.

Coronary plaque stability
The acute coronary syndromes comprise unstable angina, myocardial infarction and sudden death. An acute coronary syndrome is often the first manifestation of coronary artery disease in a previously healthy individual. In the majority of cases, the cause of acute coronary syndromes is physical disruption of an atherosclerotic plaque in a coronary artery. Our research seeks to identify markers of such "vulnerable" atherosclerotic plaque, which could be used diagnostically. We are assessing biomechanical markers measured using intravascular ultrasound and blood markers measured in samples taken from within the coronary arteries. The blood samples are also being used to study genetic determinants of unstable coronary syndromes. Our studies this year have identified promising markers in all these categories.

Contraction mediated glucose uptake as a therapeutic target in type 2 diabetes
Type 2 diabetes accounts for over 85% of diabetic patients. Our recent studies have shown that nitric oxide (NO) is an important mediator of glucose uptake during exercise. This work could contribute to novel approaches to improved diabetic control and prevention of diabetic complications.

The UK Prospective Diabetes Study provides evidence that glucose control decreases the risk of diabetes-related end points and has focussed interest on the mechanisms controlling skeletal muscle glucose uptake. Both insulin and muscle contraction increase skeletal muscle glucose uptake through translocation of the GLUT-4 glucose transporter from the cytosol to the plasma membrane. Under physiological conditions, both stimuli are important synergistic mediators of glucose uptake during exercise such that for any given level of contractile activity, insulin further increases glucose uptake.

The signalling pathways activated by insulin and contraction however differ. Patients with type 2 diabetes and insulin-resistant obese Zucker rats have impaired insulin stimulated GLUT-4 translocation, however exercise-stimulated GLUT-4 translocation is normal.

NO mediated glucose uptake
Our group has provided the first evidence for involvement of NO in contraction mediated glucose uptake in humans. In this study, infusion of a NO synthase (NOS) inhibitor during exercise in young, healthy individuals reduced glucose uptake during exercise by 48%. This study has recently been extended into type 2 diabetic patients. We have shown that NO dependent mechanisms account for 78% of glucose uptake during exercise in patients with type 2 diabetes and 34% in age, weight and fitness matched healthy individuals. The effect of NOS inhibition was significantly greater in the diabetic subjects compared with controls. Importantly, NOS inhibition had no effect on leg blood flow, arterial blood pressure, insulin or glucose concentrations during exercise. We have interpreted the data to suggest that NO mediated glucose uptake may compensate for impaired insulin action and account for the normal glucose uptake in type 2 diabetic subjects during exercise. This finding suggests that it may be possible to stimulate the contraction mediated glucose uptake pathway at rest by NO donors. We have exciting preliminary data showing that femoral arterial infusion of the NO donor sodium nitroprusside in patients with type 2 diabetes increases glucose uptake compared to the NO-independent vasodilator verapamil. Clinical trials assessing the efficacy of chronic NO donor drugs to improve glucose disposal will proceed in 2005.

CARDIAC MAGNETIC RESONANCE IMAGING

(Dr Andrew Taylor)

Cardiac magnetic resonance imaging (CMR) is a new cardiac imaging technique available at the Alfred Hospital, which provides high definition morphological and functional data of the heart. The Heart Centre has recently established a clinical and research CMR service at the Alfred Hospital in conjunction with the Department of Radiology. Since commencement of the service in 2003, over 150 CMR scans have been performed with a high rate of examination success (>95%).

The CMR service has been involved in a number of international multi-centre studies, including the OnTarget/Transend sub-studies, and also more recently the ADDUCE study which evaluates the effect of drug therapy on left ventricular mass. Smaller in-house studies are in progress that will utilise CMR to evaluate suitability of patients with heart failure for cardiac resynchronisation therapy, as well as detecting acute rejection in heart transplant recipients.

In addition, a tripartite research agreement has been signed between the Alfred Hospital, The Baker Heart Research Institute, and General Electric Corporation (USA), enabling access to CMR sequences not yet made available for commercial use, as well as enhanced technical support. This is essential to planned future in-house research projects that will develop CMR as a non-invasive tool for the evaluation of myocardial fibrosis (NH&MRC and NHF grants submitted, 2005).

CARDIOVASCULAR NEUROSCIENCE

(Professor Murray Esler)

The brain-heart link is the major focus of the group's research, conducted both in humans and in experimental animals. Our research findings support the importance of psychological mechanisms and mental stress in heart disease and high blood pressure causation.

Exploring the Mechanisms of Heart Risk in Depressive Illness
Our provisional conclusion is that the extraordinarily high level of sympathetic tone present in the heart in approximately 40% of patients with depressive illness, to the level seen in cardiac failure where high sympathetic activity contributes directly to mortality, is an important basis for the increased cardiac risk in depression.

Investigating the Neurobiology of Panic Disorder
Several important findings have emerged from studies on panic disorder. Theses include evidence of epigenetic modification (hypermethylation) of the promoter region of the noradrenaline transporter (NET) leading to reduced NE uptake and increased symptoms and risk. Evidence for a role from adrenaline co-transmission and of unique multiple salvoes of sympathetic activity in patients who suffer from panic disorder has been obtained.

Studying the Neural Pathophysiology of the Postural Tachycardia Syndrome
We are testing neural circulatory control in this common but enigmatic disorder characterised by racing heart and blackouts on standing. We describe an epigenetic (gene control) abnormality in the noradrenaline transporter gene, which seems to be the cause of the disorder. It should be noted that this abnormality is common to both POTS and panic disorder. Clinically, these two conditions often coexist.

Investigating the Neurobiology of Obesity-Related Hypertension
We are investigating the way in which the development of overweight causes blood pressure elevation, to find a rational basis for the treatment of hypertension accompanying obesity. We find that the "fat hormone", leptin is also produced in the brain in humans. Leptin release from the brain is markedly increased in human obesity, accounting for more than 25% of whole body leptin release.

Analysis of the Neurobiology of "neurogenic" essential hypertension
In preliminary studies we have begun to apply MRI methodology to investigate brain mechanisms of the form of high blood pressure initiated and sustained by overactivity of the sympathetic nervous system, "neurogenic essential hypertension".

CARDIOVASCULAR NUTRITION

(Professor Paul Nestel)

The Cardiovascular Nutrition group investigates dietary treatment and the pathophysiological consequences of metabolic disease.

The group demonstrated that dairy fat in cheese does not raise LDL cholesterol significantly in hypercholesterolaemic subjects in contrast to a similar amount of dairy fat in butter that raised LDL cholesterol substantially.

In obese subjects with metabolic complications (raised blood fats, blood pressure and insulin resistance), parameters of sympathetic nervous system activity were found to be elevated compared with lean subjects. However after modest weight reduction sympathetic overactivity diminished (as measured by production of noradrenaline and direct signals from nerves) and this improvement paralleled better glucose utilisation, lower blood pressure and lower blood fats.

VASCULAR PHARMACOLOGY

(Dr Jaye Chin-Dusting)

Soluble P-Selectin in cardiovascular disease
P-selectin is a member of the selectin family and is localized in the membranes of the α-granules of platelets and the Weibel-Palade bodies of endothelial cells. P-selectin supports adhesion of leukocytes to activated platelets present in thrombi or to activated endothelial cells, where it mediates leukocyte rolling, part of the adhesion cascade, therefore making it an attractive therapeutic target, especially for vascular diseases.

We now confirm our initial observations that soluble P-selectin increases neutrophil adhesion to spread platelet monolayers and further that soluble P-selectin mediates increases in monocyte adhesion to spread platelet monolayers. Preliminary Soluble P-selectin signalling events have also been examined, uncovering the importance of both PSGL-1 and Src on soluble P-selectin mediated neutrophil adhesion to platelets. The effects of soluble P-selectin on thrombus formation over both collagen and von Willebrand factor (VWF) have been examined; soluble P-selectin increases thrombus formation on VWF.

The isoflavone metabolite dehydroequol produces vasodilatation in human resistance arteries via a nitric oxide-dependent mechanism
Isoflavones (phytoestrogens) offer potential cardioprotective benefits. We recently reported on the vasodilatory activity of the isoflavone metabolite, dehydroequol, in rat isolated aortic ring preparations. In the current study, we examine the effect of this metabolite on the vascular haemodynamic profile in human forearm resistance arteries.

This is the first report of dehydroequol, a metabolite derived from the isoflavone diadzein, demonstrating potent vasodilatory properties in human resistance arteries via a nitric oxide-dependent mechanism.

Plasma C-reactive protein, but not protein S, VCAM-1, von Willebrand factor or P-selectin, is associated with endothelium dysfunction in coronary artery disease.
Abnormal endothelium-dependent vasodilatation is well documented in coronary artery disease (CAD), as are significant increases of acute phase inflammatory proteins and other soluble hepatic and endothelium derived proteins. In the current study we investigated whether there is a relationship between endothelium-dependent vasodilatation and the plasma levels of such proteins. Further we examined the association between these proteins, together with age, cholesterol and endothelium function, and participant status (i.e. healthy, smoker, coronary artery disease).

We conclude that there is an inverse correlation between C-reactive protein, but not protein S, VCAM-1, P-selectin nor von Willebrand factor, levels and abnormal endothelium-dependent vasodilation and further that responses to acetylcholine together with C-RP protein have a strong association with cardiovascular risk and disease.

HUMAN VASCULAR BIOLOGY

(Prof Stephen Duffy)

Relationship of Iron Status to Oxidative Stress in vivo, Nitric Oxide Bioactivity and Coronary Artery Disease Activity
Patients with high total-body iron levels may be at higher risk for the development of atherosclerosis and coronary artery disease. Endothelial-derived nitric oxide (EDNO) is an important anti-atherosclerotic molecule, and its activity is decreased in patients with coronary artery disease. In this study we are testing the hypothesis that acutely increasing extracellular iron concentration will attenuate EDNO bioactivity in the peripheral vasculature of healthy volunteers and patients with coronary artery disease.

Reactive oxygen species have been implicated in the pathogenesis of atherosclerosis. Redox-active iron increases production of reactive oxygen species (via Fenton chemistry) and causes lipid peroxidation. F2-isoprostanes are a reliable method for assessment of oxidant stress in vivo. We aimed to determine the relationship of these markers of oxidative stress in coronary blood samples to clinical presentation and plaque characteristics.

The Role of Non-prostanoid, Non-nitric oxide, Endothelium Derived Factors in Patients with Cardiovascular Disease
We have previously demonstrated that endothelium-derived vasodilators such as nitric oxide and prostacyclin contribute to metabolic vasodilation in skeletal muscle and coronary artery vasculature. In vascular smooth muscle cells, efflux of K+ through large-conductance Ca-sensitive K+-channels and ATP-sensitive K+-channels results in hyperpolarization, relaxation and consequent vasodilation.

In this study we have shown that the forearm vasodilator response to acetylcholine was impaired in patients with coronary artery disease (CAD) compared to that of healthy volunteers. The data suggest that tonic activation of Ca-dependent K+-channels contributes to resting blood flow in skeletal muscle vasculature in health, but not in patients with CAD.

We are currently investigating the contribution of Ca-dependent K+-channels in the absence of NO and prostacyclin, two other important vasodilators that can cause vascular smooth muscle cell hyperpolarization. The data suggest that activation of Ca-dependent-K+-channels does not contribute to agonist-induced vasodilation in the skeletal muscle vasculature of humans.

Nitric Oxide and Oxidant Stress in Human Hypertension
In this NHMRC funded (Project Grant) study we are testing the hypotheses that hypertension in humans, including low-renin hypertension, is associated with increased oxidative stress, and that amelioration of this oxidative stress with the antioxidant ascorbic acid will lower blood pressure by increasing nitric oxide bioactivity.

Prevention of the No-reflow Phenomenon in Acute Coronary Syndromes
The "no-reflow" phenomenon occurs in 30% to 40% of cases of acute myocardial infarction despite no residual stenosis at the original site of coronary occlusion after percutaneous transluminal coronary angioplasty (PTCA) and stenting, and is associated with a poor prognosis. The aim of this prospective, randomised study is to determine whether the vasodilators sodium nitroprusside (SNP) and verapamil will improve coronary blood flow, coronary flow reserve and reduce myocardial infarct size in patients with myocardial infarction.

The data suggest that SNP is an effective and safe treatment for no/slow-reflow in the setting of PCI for MI. Prospective, randomised studies will be required before this therapy can be recommended generally.

Melbourne Interventional Group Database
This is a co-operative database of percutaneous revascularization procedures that includes most of the Victorian public hospitals that perform coronary interventions. Our ultimate aim (with respect to the database) is to obtain short & long-term outcomes of coronary interventions for all patients in the state, though we are currently obtaining a representative sample. A number of abstracts with preliminary data have been submitted to the Cardiac Society of Australia & NZ annual scientific meeting for 2005. An additional aim is to provide a framework to complete interventional/clinical trials.

PROJECTS WITH CURRENT (2004) ALFRED ETHICS COMMITTEE APPROVAL

Aggarwal A, Dart A, Kingwell B. The effect of Angiotensin Converting Enzyme Inhibitor on aortic wall properties in patients with Marfan Syndrome.

Chin-Dusting J, Williams C. Therapeutic Restoration of Endothelium Dysfunction Targeted Towards Hypercholesterolemics with Nitric Oxide Synthase Polymorphism.

Chin-Dusting J. A double-blind, randomized, multi-centre study to investigate the safety, tolerability and effects of tezosentan on portal pressure in patients with portal hypertension secondary to cirrhosis.

Chin-Dusting J. Preventive use of probiotics in chronic liver disease with portal hypertension, effect on circulatory changes and hepatic encephalopathy: proof of concept study.

Dart A, Chin-Dusting J. Comparison of the effects of milk containing beta casein A1 or A2 in the diets of persons at high risk of cardiovascular disease on surrogate markers of disease development.

Dart A, Schneider L. Atrial fibrillation Clopidogrel trial with Irbesartan for prevention of Vascular Events. A parallel randomized controlled evaluation of clopidogrel plus aspirin, with factorial evaluation of irbesartan, for the prevention of vascular events in patients with atrial fibrillation.

Dart A, Williams C. Cardiovascular disease and its genetic correlation with pseudoxanthoma elasticum.

Dart A, Williams C. Genetic analysis of risk of atherosclerosis and cardiovascular disease.

Dart A. A multinational, multicentre, randomised, double blind, placebo controlled clinical trial with a mean follow-up of five years in at least 6000 patients with chronic symptomatic coronary artery disease (angina pectoris).

Dart A. A randomized double-blind trial of omega-3 fatty acid supplementation for the treatment of anti-retroviral induced hypertriglyceridaemia in HIV infected males.

Dart A. Adult bone marrow derived angioblasts for revascularization of ischaemic myocardium.

Dart A. An open-label, randomised, multi-centre, phase IIIb, parallel group switching study to compare the efficacy and safety of lipid lowering agents atorvastatin, pravastatin, simvastatin, cerivastatin and rouvastatin in subjects with type II a and IIb hypercholesterolaemia. (Mercury 1 study 45221L/0081).

Dart A. HS-CRP and its association with vascular events in HIV positive patients.

Dart A. Non-invasive assessment of arterial properties.

Dart A. Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT).

Dart A. The effect of LDL-cholesterol lowering beyond currently recommended minimum targets on coronary heart disease (CHD) recurrence in patients with pre-existing CHD.

Duffy S. Effects of polymorphisms in antioxidant genes on the clinical presentation (stable versus unstable coronary syndrome) in a group of patients undergoing coronary angiography.

Duffy S. Relationship of iron status to oxidative stress in vivo and nitric oxide bioactivity.

Duffy S. Vitamin C for Treatment of Hypertension: a Randomized, Placebo-controlled Study.

Esler M, Lambert G, Kaye D. The neurobiology of depressive illness: causes and consequences of altered brain monoaminergic function.

Esler M, Lambert G, Schlaich M, Kaye D. The neurobiology of essential hypertension: pathophysiological mechanisms of increased sympathetic activity in hypertensive subjects.

Esler M. In vivo microdialysis studies of metabolite and neurotransmitter overflow from the adipose tissue and skeletal muscle.

Jennings G, Reid C. On Target: ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial and Transcend: Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease.

Jennings G. A prospective, randomised, open-label, blinded end-point, forced-titration trial to compare MICARDIS PLUS.

Jennings G. Clinical utility of Amlodipine/Atorvastatin to improve concomitant cardiovascular risk factors of hypertension.

Kaye D, Esler M, Schlaich M. L-arginine transport and its role in impaired endothelium dependent vasodilation in essential hypertension.

Kaye D, Gould P. An investigation into the effect of biventricular pacemakers on chronic sympathetic activity in congestive heart failure.

Kaye D, Gould P. An investigation into the effect of exercise on sympathetic activation in congestive heart failure patients with atrial fibrillation and the effect of atrial fibrillation on baroreceptor response in congestive heart failure.

Kaye D, Williams C. Isolation and identification of the causative gene defect in a family with dilated cardiomyopathy using genome wide screening and microsatellite markers.

Kaye D. An investigation in to the ability of the body to re-innervate the heterotopic cardiac graft.

Kaye D. An investigation into the effect right ventricular pacing on sympathetic activation in patients with decreased left ventricular function.

Kaye D. Coenzyme Q10 as adjunctive treatment of chronic heart failure. A randomised double-blind multicentre trial with focus on SYMptoms, Biomarker status (BNP) and long-term Outcome (hospitalisation/mortality) (Q-SYMBIO).

Kaye D. Evaluation of the VentrAssist Left Ventricular Assist System (LVAS) in patients with end stage heart failure.

Kaye D. Evaluation of the VentrAssistTM left Ventricular Assist System as a Bridge to Cardiac Transplantation Trial Number: CP023001.

Kaye D. Evaluation of the VentrAssistTM left Ventricular Assist System as Destination Therapy Trial Number: CP024001.

Kaye D. Exercise training in heart failure: effects on exercise capacity, quality of life, neurohormones and body composition.

Kaye D. The effects of insulin on L-arginine transport in the human forearm.

Kaye D. To examine the influence of right ventricular versus biventricular pacing on sympathetic tone, brain naturetic peptide, endothelin and haemodynamics in heart failure patients undergoing biventricular pacemaker implantation.

Kaye D. Research study using the cardiac dimensions, inc (CDI) percutaneous mitral annuloplasty device for the temporary plication of the mitral annulus in a dilated cardiomyopathy patient population Protocol CVP –0894-01.

Kingwell B, Duffy S. Contraction mediated glucose uptake as a therapeutic target in type 2 diabetes.

Kingwell B. A novel mechanism mediating anti-atherosclerotic and metabolic actions of HDL cholesterol.

Kingwell B. Effect of ace inhibition on walking distance, endothelial function and blood flow during exercise in patients with peripheral arterial disease.

Kingwell B. Effect of fitness on chronic low-grade activation of the immune system and insulin sensitivity in physically fit and healthy sedentary individuals.

Kingwell B. Metabolic regulation of ABCA1 expression in patients with type 2 diabetes and athletes.

Krum H, Taylor A. A randomised, double-blind, placebo-controlled, dose-ranging pilot study of the efficacy and safety of CC811007 in subjects with type 2 diabetes mellitus and heart failure (ADDUCE).

Lambert G, Lambert E, Darwood T. Depression and the heart: the influence of depression on the success of cardiac rehabilitation.

Nestel P. A randomised, double-blind, placebo-controlled, cross-over pilot study to define the high density lipoprotein (HDL) cholesterol-raising mechanism of rosuvastatin (CRESTOR) by quantifying the key steps in reverse cholesterol transport.

Nestel P. A study of the effects of dietary energy restriction and weight loss on sympathetic nervous system activity, insulin sensitivity and cardiovascular risk in metabolic syndrome patients with central obesity.

Nestel P. Do cheese and butter at equivalent fat intake affect cardiovascular risk similarly?

Nestel P. Effect of the isoflavone metabolite trans-tetrahydrodaidzein on cardiovascular risk factors in middle-aged subjects.

Nestel P. Effects of dietary phytosterols on the kinetics of apolipoprotein B in obese subjects.

Pepe S, Van den Brink, O. Measurement of opioid proteins in blood from patients undergoing cardiac surgery.

Reid C, Head G, Jennings G. Improved method for analysing ambulatory blood pressure (BP) and heart rate (HR) data.

Reid C. A survey of Eating-behaviour and school-community based Nutrition-Health Promotion, programs and policies.

Reid C. Short and long term follow up of interventional cardiology procedures at the Alfred Baker Medical Unit (ABMU).

Reid C. The use and misuse of aspirin-An audit of the use of Aspirin in Hypertension.

Schneider L, Dart A, Chin-Dusting J, Kingwell B. Diurnal variation in endothelial function in patients with two or more treated risk factors for ischaemic heart disease.

Shaw J. Does systemic arterial compliance predict blood pressure responses in patients undergoing percutaneous angioplasty.

Sviridov D, Dart A. Understanding of the mechanisms of lipid dysregulation in HIV-infected patients.

White A, Dart A, Duffy S, Cameron J, Kingwell B. Plasma inflammatory markers, matrix metalloproteinases and biomechanical properties in coronary artery plaque stability.

Woollard K, Chin-Dusting J, Dart A. Soluble P-selectin levels in peripheral arterial occlusive disease (POAD).

POST GRADUATE STUDENTS

Anna Ahimastos, B biomed Sc (Hons) PhD (Monash)
Edna Bajunaki PhD (Melb Uni)
David Barton PhD
Nathan Connelly MBBS, FRACP PhD Student
Tye Dawood PhD Student
Michael Ditiatkovski, B Sc (Hons) PhD Student
Brian Drew, BSc (Hons) PhD (Monash)
Karen Fang PhD (Melb Uni)
Christine Goh PhD (Finished 2004)
Paul Gould, MBBS, FRACP, DDU PhD (Monash)
Darren Henstridge, BSc (Hons) PhD (Monash)
Ngan Huynh PhD
Chenyi Lo MS (Melb Uni)
Greta Meredith PhD (Finished 2004)
Swati Mikherjee MBBS, PhD Student
Andrew Murphy PhD
Rajesh Nair MBBS, MRCP (UK) PhD Student
Ruchi Patel PhD
Tina Raj, B Sc (Hons) PhD Student
Helen Rancie PhD (Finished 2004)
Christopher Tefft BSc (Hons) Monash (Graduated 2004)
Kelly To, B Sc (Hons) PhD Student
Kamble Wang MS (Melb Uni)
Anthony White, MBBS PhD (Monash)
Geoffrey Wong MS (Melb Uni)

COMPETITIVE GRANTS (2004)

Duffy, SJ. NHMRC Project Grant. Nitric oxide and oxidant stress in hypertension. 2003-2005: $80,000.

Jennings G, Bobik A, Dart A, Esler M, Kaye D. Heart failure and its antecedents. NHMRC Program Grant. 2003-2007: $8,875,000.

Jennings G, Dart A, Esler M, Kaye D, Chin-Dusting J, Kingwell B, Reid C. ABMU Centre for Clinical Cardiovascular Research. NHMRC CCRE Grant. 2003-2007: $2,000,000.

Kaye D, Power J, Jois M. Mechanisms and therapy of cardiac cachexia. NHMRC Special Initiatives Grant. 2002-2004: $120,000.

Kingwell, B A. & Duffy, S J. Diabetes Australia Research Trust, A novel mechanism by which HDL cholesterol may modulate glucose and fat metabolism 2005: $45,000.

Kingwell B, Duffy S, McConell G. NHMRC project, A novel mechanism for manipulation of peripheral glucose disposal in patients with Type 2 diabetes. 2004–2006: $279,950.

AWARDS

RT Hall Prize (CSANZ):
To: Professor A Dart, A/Prof B Kingwell, Dr C Gatzka and Dr J Cameron: For studies in Arterial Biomechanics.

The Inaugural Phillips Ormonde & Fitzpatrick Cardiovascular Award:
To: Dr Jaye Chin-Dusting: For the collaborative work done with Aus-Bio Ltd

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