INTRODUCTION

(Prof Anthony M Dart)

The department of Cardiovascular Medicine continues to undertake research ranging from studies into the basic mechanisms of disease through to evaluation of clinical practice. The majority of studies reported have been performed on collaboration with a number of colleagues, both within and outside the department. In the interests of brevity the report has not listed these individually.

Several developments during the year have considerably strengthened the research capability of the department. Notable amongst these have been considerable work in relation to peripheral vascular disease and expansion of our clinical and research programme in cardiac MRI. Recruitment of new staff has given us the opportunity to initiate and extend research into atrial fibrillation, an increasing clinical problem. The acquisition of our new catheter laboratories with electrophysiological capability has been a crucial step in allowing the department to develop a research interest in this area. Similarly the upgrading of our echocardiographic equipment has made it feasible for the department to plan for a range of studies previously not possible.

NONINVASIVE CARDIAC SERVICES

(Dr Jack Federman)

The Heart Centre has had major involvement in the following research studies during 2006.

  1. Veritas Study: This study involves the placement of a percutaneous mitral annular clip device to reduce mitral regurgitation in patients with poor left ventricular function. Echocardiograms are performed before the procedure to select suitable patient and quantify the degree of mitral regurgitation with echocardiography studies being performed during the procedure to assess the response to various degrees of tension on the mitral annular device. Follow up echocardiography studies are then performed to assess the subsequent benefits of the device with regard to the degree of mitral regurgitation and left ventricular function.
  2. Triple R Study: This study involves the evaluation of patients who require resynchronisation therapy for poor left ventricular function with a left bundle branch block. These patients are evaluated with a cardiac MRI and an echocardiography and Doppler study prior to insertion of a biventricular pacemaker. The benefits of therapy are then further assessed post procedure using echocardiography.
  3. Study on left ventricular strain and diastology in cardiac transplantation patients: Cardiac transplantation patients are being assessed using echocardiography including tissue Doppler, strain and strain rate imaging to better evaluate diastolic function.
  4. Patent foramen ovale closure with a percutaneous device in patients with unexplained cerebral vascular events from other causes: These patients are having an Amplatzer patent foramen ovale closure device placed in the cardiac catheter laboratory under radiological and echocardiography guidance. The adequate positioning of the device and successful closure of patent foramen ovale are then assessed by echocardiography.
  5. Assessment of diastolic function and vessel compliance in diabetes mellitus: This study involves the use of echocardiography to assess diastolic function in patients with type I and type II diabetes and a normal control group.

The Heart Centre has also been involved in performing echocardiograms in the following studies which have been performed by other units.

  1. Morbid obesity study: Morbid obese subjects are being evaluated for cardiac function and cardiovascular risk profiles following substantial weight loss. They are having a full echocardiogram and studies of the intimal/medial thickness of their carotid vessels.
  2. Ideal study: This study involves the assessment of left ventricular function by echocardiography to try to determine the optimum time to commence dialysis in patients with chronic renal failure.
  3. Co-enzyme Q10 study: This study involves the use of echocardiography to assess the changes in cardiac function in heart failure patients given treatment with co-enzymes Q10.
  4. Ultrafine study: This study involves the use of echocardiography to assess the cardiac effects of ultrafine particles in the air. There is also a respiratory assessment of patients as well.
  5. Homeostasis study: This study uses echocardiography to assess cardiac function in patients with severe heart failure who have guided home self therapy.

Other studies in which the Heart Centre has been involved include.

  1. Bone marrow transplant study: These patients are having regular exercise stress tests to assess exercise capacity in patients having bone marrow transplantation.
  2. BNP trial: This study involves an assessment of the serum BNP levels in patients presenting to the Emergency Department with symptoms of shortness of breath. A review of the clinical data is then being made following hospital discharge to ascertain whether the patient did or did not have evidence for heart failure at the time of their presentation.

INTERNATIONAL COLLABORATIVE TRIALS

FREEDOM: This study is evaluating patients with Diabetes Mellitus who have multivessel coronary artery disease and comparing coronary artery bypass surgery with insertion of drug eluting stents in the diseased arteries. The current recommended therapy for such patients is coronary artery bypass surgery. The use of multiple drug eluting stents has not been studied specifically in diabetic patients with multivessel coronary artery disease. The study involves 2,400 research participants in medical centres in the US, Canada, Europe, Sth America, Australia, and New Zealand.

RE-LY: This study is evaluating patients with uncomplicated Atrial Fibrillation, comparing Warfarin and a direct thrombin antagonist. This potentially will achieve the same benefit as Warfarin but at a fixed dose and without the need for regular blood tests to monitor INR.

ILLUMINATE: This trial was testing a new drug (Torceptrapib) that increases HDL cholesterol ("good" cholesterol). This was tested in patients with diabetes or coronary artery disease. The trial was terminated early on advice from the Data and Safety Monitoring Committee due to excess mortality in the treatment arm.

BEAUTIFUL: This trial will examine the effects of Ivabradine in patients with coronary artery disease and impaired heart function. Ivabradine decreases heart rate and has been shown to decrease the frequency of chest pain and allows patients to exercise for longer periods of time. The purpose of the study is to evaluate whether Ivabradine reduces cardiovascular events when given in addition to usual treatment for heart disease.

SHINE: This study is evaluating the dose effect of a new anticoagulant drug in patients who are hospitalised with angina or a heart attack and are scheduled for an angioplasty.

CHAMPION Study
This is a study sponsored by the Medicines Company of the short-acting, intravenous anti-platelet agent Cangrelor versus high-dose oral clopidogrel in patients with coronary artery disease undergoing percutaneous coronary revascularization.

LABORATORY OF CARDIOVASCULAR NUTRITION

(Prof Paul Nestel, Dr Dmitri Sviridov)

Work has continued in relation to HDL function and the existence of dysfunctional HDL. In recent study this was examined in the metabolic syndrome.

A notable finding was that when HDL from these subjects were incubated with cholesterol-loaded human macrophages the net flow of cholesterol was paradoxically from HDL into macrophages (resembling the findings with LDL), whereas our previous studies with HDL from lean, healthy men had always shown flow of cholesterol from cells to HDL.

This unexpected finding may have reflected the preponderance of smaller HDL containing the LpA-I/A-II species, since following treatment with a statin there was an increase in the large LpA-I particles and a concomitant diminution in the abnormal cholesterol flux. The improved profile in HDL apolipoprotein composition after statin was related to several factors: reduction in apolipoprotein B lipoproteins (LDL and VLDL) which exchange lipids with HDL, and reductions in the cholesterol ester transfer protein (CETP) and esterifying enzyme (LCAT) which mediate cholesterol transport.

This is the first demonstration of HDL dysfunctionality in subjects with metabolic syndrome, as manifested by abnormal cholesterol transport between HDL and cells.

CLINICAL PHYSIOLOGY

(Associate Professor Bronwyn Kingwell)

Perindopril reduces large artery stiffness and aortic root diameter in patients with Marfan syndrome.
Aortic stiffness is elevated in Marfan syndrome (MFS) contributing to aortic dilatation and rupture, the major cause of premature death in this population. Given the known beneficial effects of angiotensin converting enzyme inhibitors (ACEIs) on arterial stiffness, the effect of perindopril therapy on aortic stiffness and aortic dilatation in MFS patients was examined. MFS patients on standard β-blocker therapy were randomised to also receive either perindopril or placebo for 24 weeks in a randomised, double blind study. Indices of arterial stiffness were assessed globally and regionally. Aortic root diameter was assessed via a transthoracic echocardiogram. Perindopril reduced both arterial stiffness and aortic root diameter. While perindopril marginally reduced mean blood pressure, importantly, the observed changes in both stiffness and aortic diameter remained significant when mean blood pressure was included as a covariate.

Thus ACEIs reduce aortic stiffness and aortic root diameter in MFS patients and may potentially protect against aortic rupture.

Novel activators of AMP-kinase as potential therapies for type 2 diabetes.
AMP-activated protein kinase (AMPK) is a key metabolic enzyme, responding to low levels of energy by increasing energy production via increased glucose uptake and fatty acid β-oxidation. Therefore, activators of AMPK are potential candidates for the therapy of type 2 diabetes mellitus (T2DM). New mechanisms of AMPK activation were examined using two novel compounds in human primary skeletal muscle cell culture.

Vastus lateralis muscle biopsies were obtained from healthy male controls and males with T2DM. Two novel agents stimulated glucose uptake and fat oxidation in primary human skeletal muscle cultures obtained from biopsy, through direct activation of AMPK. Glucose uptake was increased relative to basal glucose uptake for the respective cell types in both healthy and T2DM cells. These responses were equivalent to that observed with a pharmacological dose of insulin. Bak02 induced glucose uptake only in T2DM cells.

In conclusion, these data clearly demonstrate that both new agents activate AMPK to increase glucose uptake and fatty acid oxidation in human primary skeletal muscle cell culture.

Matrix metalloproteinase-3 genotype is associated with higher coronary plaque burden, positive remodeling and increased risk of unstable disease.

The matrix metalloproteinases (MMPs) are enzymes responsible for modulating the protein scafffolding between cells and are plausible candidates for susceptibilility to acute coronary syndrome. The possibility that common MMP polymorphisms would relate to corresponding MMP plasma levels, coronary plaque characteristics and unstable clinical presentation was examined. Patients with de novo presentation of coronary artery disease undergoing coronary angiography were classified into unstable coronary syndrome and stable angina pectoris groups using Braunwald criteria. Patients were genotyped for 4 common MMP promoter polymorphisms. Plaque characteristics were assessed in a sub-group of 40 patients using intravascular ultrasound. The 6A allele of the MMP-3 polymorphism was associated with unstable clinical presentation. Furthermore, 6A allele carriers had higher plasma MMP-3 concentration, maximum coronary stenosis, plaque area, percentage plaque burden and remodeling ratio. Other genotypes did not relate to either plaque characteristics or clinical presentation. Thus the MMP-3 6A allele promotes positive coronary remodeling associated with greater plaque burden and increased susceptibility to unstable coronary syndromes in humans.

Ramipril reduces large artery stiffness and improves walking ability in patients with peripheral arterial disease; a causal relationship?
A Framingham sub-study has shown that large artery stiffening may reduce peripheral blood flow through elevation in pulse pressure which impairs endothelial function and microvascular reactivity. Previous studies from the department showed that the ACE inhibitor ramipril reduced arterial stiffness and increased maximum walking time by over 200% in patients with peripheral arterial disease (PAD). It was note clear however whether these were related.

Forty PAD patients were randomised to ramipril, 10 mg once daily or placebo for 24 weeks in a randomised, double blind study. Maximum walking time was recorded during a standard treadmill test. Indices of arterial stiffness were assessed.

Ramipril increased maximum walking time, and reduced arterial stiffness as assessed by SAC compared with placebo. There were moderately strong correlations between the pre/post intervention change in maximum walking time and the change in indices of arterial stiffness. Simple modelling suggests that the major site of wave reflection was moved distally by ramipril. In conclusion, these relationships are likely to be partly accountable by independent effects of ramipril on both the large and small arteries.

VASCULAR PHARMACOLOGY

(Dr Jaye Chin-Dusting)

Endothelial cell type and activation state affects sP-selectin mediated adhesion.
Leukocyte adhesion via P-selectin to an activated endothelium is known to participate in both peripheral and coronary atherosclerosis. The soluble version of P-selectin is increased in both these states and has been shown to be biologically active in peripheral occlusive arterial disease, in inducing leukocyte adhesion to platelets. In the current study the effects of sP-selectin on leukocyte adhesion to endothelial cells and further whether endothelial cell type and the activation state matter were examined. sP-selectin mediated leukocyte adhesion under shear stress to resting and TNF-α (4ng/ml; 24hrs) activated endothelial cells from human umbilical vein (HUVEC), coronary (HCAEC), iliac (HIAEC), microvascular arterial (HMAEC) were compared using a circular parallel plate flow chamber. Recombinant sP-selectin-Fc (150ng/ml) significantly increased neutrophil adhesion under shear (150s-1) to resting but not TNF-α activated HUVEC. There were no significant differences in unstimulated neutrophil adhesion between resting endothelial cell types. However after TNF-α activation both HUVEC and HMAEC showed significantly higher increases in adhesion compared with HCAEC and HIAEC. This was also evident after sP-selectin neutrophil activation. In order to extend these studies into a functional in-vivo environment isolated neutrophils were fluorescently labelled and perfused (0.12mls/min) through dissected mouse aorta under physiological conditions. As shown in-vitro, sP-selectin significantly increased neutrophil adhesion as analysed using epi-fluorescence microscopy. In summary, endothelial cell type affects the extent of sP-selectin induced leukocyte adhesion. Further sP-selectin consistently increases leukocyte adhesion to resting but not activated endothelial cells. These studies demonstrate that sP-selectin may influence the early progression of vascular disease before endothelial dysfunction and highlights the influence of endothelial cell type on leukocyte adhesion.

CARDIAC MAGNETIC RESONANCE IMAGING

(Dr A Taylor)

Cardiac magnetic resonance imaging (CMR) provides high definition morphological and functional data of the heart, as well as information on tissue composition. 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 400 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/Transcend sub-studies, and also more recently the ADDUCE study which evaluates the effect of drug therapy on left ventricular mass. Smaller in-house studies have utilised CMR across a broad range of clinical applications, including the evaluation of the suitability of patients with heart failure for cardiac resynchronisation therapy, diagnostic utility in arrythmogenic right ventricular dysplasia, the detection of acute rejection in heart transplant recipients, changes in cardiac morphology in obesity with rapid weight loss, and CMR-guided left ventricular remodelling surgery. Recently, a large study investigating the non-invasive evaluation of myocardial fibrosis with CMR in heart failure, as well as its relationship with diastolic dysfunction, has commenced. Alfred CMR research has already been presented in abstract form at the CSANZ Scientific Sessions 2006, with 5 new abstracts submitted in 2007, as well as a number of manuscripts currently undergoing peer review. The CMR service has attracted 2 international research fellows, with a local PhD student commencing in January 2007.

A tripartite research agreement exists 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. In addition in 2006 the Alfred Clinical CMR service was awarded a New Technology Grant from the Department of Human services, Victoria for $350,000/year for the next 2 years, which will expand available CMR time to approximately 500 CMR scans per year.

THE HUMAN NEUROTRANSMITTERS LABORATORY

(Dr Gavin Lambert)

Exploring the heart-brain link
Our Laboratory has been investigating several disorders that impact on heart health. Postural Tachycardia Syndrome, or POTS, is a condition that has only been recently identified in medical literature. The disorder most commonly affects young women, but older people, including men, can also be afflicted. It is characterised by fatigue, palpitations, exercise intolerance, light- headedness, visual blurring, inability to concentrate and episodic fainting. Many of these symptoms are prevalent in other disorders, so it is important to realise that one, or more, of the symptoms described does not necessarily lead to a diagnosis of POTS. Unexplained recurrent fainting is most commonly due to a disorder of circulatory control, of which there are many in addition to POTS, and are a frequent cause of visits to the general practitioner.

A hallmark of POTS is that during fainting, blood pressure is maintained, or only falls minimally, while heart rate increases dramatically. The onset of POTS is often abrupt and in about 50% of cases, follows an infection. POTS appears to be a manifestation of overactivity of the sympathetic nervous system, the system involved in making the heart beat harder and faster. One of the most effective ways of diagnosing POTS is tilt table testing, which we perform at the Heart Centre. This test involves heart rate monitoring and inserting a catheter into the artery for accurate blood pressure measurement, and for blood sampling, at different degrees of tilting. Simultaneous recording of muscle sympathetic nerve activity also provides important diagnostic information. We have made significant progress in obtaining information that will help us identify the possible cause(s) of POTS and possible treatment options for sufferers.

In addition, findings from our Metabolic Syndrome study have shown that not only are the different variables of the Metabolic Syndrome detrimental to the heart, but that whole body insulin sensitivity is also significantly associated with whole body sympathetic activity. To expand on some of our novel findings, we are now investigating the effects of diet and exercise on Metabolic Syndrome variables and how they modify the risk of heart disease.

Our ongoing work in depressive illness and panic disorder has produced some interesting, and somewhat unexpected, results. Despite popular belief, we found that the brain chemical serotonin is increased in people with panic disorder, with higher levels being associated with increased severity of the disorder. Following treatment with an SSRI, a type of antidepressant, brain serotonin levels decreased significantly. The effect of SSRI's on the risk of heart disease is also being investigated. In depressive illness, we observed that factors involved in inflammation are elevated, increasing the risk of heart attacks. We are now examining possible pathways for this observation and how SSRI's might modify risk of heart disease in depressive illness.

We are appreciative to all our study volunteers in helping us collect data.

SECONDARY PREVENTION

The COACH Program (Sarah Ballis, Cardiac Coach)

The year 2007 sees The COACH Program in its fifth year of operation at The Alfred hospital. Since the implementation of the program at this site in December 2003 over 600 Alfred patients have received "coaching" to assist them in achieving the National Heart Foundation of Australia target levels for their biomedical coronary risk factors as well as to take recommended cardiovascular medications.

The COACH Program is a telephone delivered disease management program that works to reduce risk factors in patients with coronary heart disease (CHD) as demonstrated by the highest level of evidence - a multi-centre randomised controlled trial.

Since its conception The COACH Program has consistently shown positive results for patient outcomes. A three year analysis of outcomes from the four Melbourne hospitals which operate The COACH Program as part of conventional care, demonstrated that coached patients made significant improvements in all of their CHD risk factors including total cholesterol, LDL cholesterol, blood pressure, smoking cessation, exercise and medication adherence. Results have also shown that coaching in CHD can reduce hospital readmissions and beddays by 16% and 20% respectively.

In 2006 the Royal Melbourne hospital site took an innovative and leading role in the expansion of COACH into new disease areas and in culturally and linguistically diverse (CALD) communities. Coaches at the RMH have commenced coaching patients with metabolic syndrome and in addition have developed a protocol for the coaching of Greek speaking clients through the use of trained interpreters. The observed success in these new areas demonstrates the ability of The COACH Program to be moulded to fit any disease state which has measurable risk factor outcomes and target levels. Plans for the expansion into diabetes risk factor management and chronic obstructive pulmonary disease are underway.

It is hoped that in the future The Alfred site will be able to follow suit and continue to expand The COACH Program into new health areas which may too prove to reduce hospital admissions and improve patient outcomes.

HEART FAILURE AND TRANSPLANT RESEARCH

(Professor David Kaye)

The management of patients with severe heart failure is a major focus of the Alfred Cardiology Department. The Unit acts as the quaternary referral centre, being responsible for the delivery of complex medical, surgical and device based therapies in partnership with the Cardiothoracic Surgery Department at the Alfred. In conjunction clinicians and scientists at the Alfred, Baker Institute and Monash medical school continue to be very active in research the pathophysiology of heart failure and as a product developing new treatments.

Research into several novel devices for the treatment of heart failure has progressed well during the year. These including the completion of the trial of the Ventracor artificial heart device in patients requiring subsequent heart transplantation. We also have commenced a study of a permanent percutaneous device for treatment mitral regurgitation in heart failure patients and have implanted several patients with a novel system for measuring pressure inside the heart as a guide to lung congestion.

In more mechanistic research work, we have been investigating the role that circulating 'stem' cells play in heart failure patients, how they interact with the heart and in identifying the chemical signals that determine their activity.

In the area of heart transplantation, Dr Angeline Leet has been actively investigating the influence of newer immunosuppressive drugs on clinical outcome. She has also developed a programme of studies on cardiac fibrosis, a particular problem late after transplant.

PERIPHERAL INTERVENTIONAL PROGRAM

(Dr James Shaw)

The Alfred Minimally Invasive Vascular Centre (AMVIC) works as a collaboration between the cardiology and radiology departments. This group has a specific interest in the management of non-coronary vascular disease with an emphasis on novel endovascular therapies.

Current research projects include examining potential predictors of blood pressure improvement following renal artery stenting. This study has enrolled 27 patients 25 of whom have completed 6 month follow up. Interim analysis has shown an improvement in blood pressure in the patients undergoing renal artery stenting but disappointingly no useful predictors of improvement have been seen. This work has been submitted for presentation at the Australian New Zealand cardiac society meeting in August 2007. We are also the main Australian site for the international CORAL trial which will compare medical therapy with renal artery stenting in patients with renovascular disease. The endpoints in this study will include progression to renal failure, blood pressure control and all cause mortality.

The other major area of research involves examining the effects of Intravenous HDL on atherosclerotic plaque composition in patients undergoing lower limb percutaneous revascularisation for symptom limiting claudication. Patients scheduled for percutaneous lower limb revascularisation are pre-treated with an infusion of HDL. Several days later peripheral artery angioplasty and artherectomy is performed yielding tissue for subsequent histological, biochemical and immuno-histochemical analysis. A matched control group recovers a placebo infusion. Recent IVUS trial data showed a promising response to this therapy in coronary arteries so that further elucidation of the effects of such therapy on biochemical change will be of great interest.

HUMAN VASCULAR BIOLOGY LABORATORY

(Dr Stephen J Duffy)

Melbourne Interventional Group
This is a co-operative database of percutaneous revascularization procedures that includes seven of the Victorian public hospitals that perform coronary interventions. Our ultimate aim is to obtain short- & long-term outcomes of coronary interventions for all patients in the state. Currently more than 5,000 patients have been entered into this database, and 30-day and 12-month follow-up is available for more than 4,500 and 2,500 patients at these respective time points. An additional aim is to provide a framework to complete interventional/clinical trials.

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. In animal models of atherosclerosis, iron has been shown to contribute to the progression of disease development. Endothelial-derived nitric oxide (EDNO) is an important anti-atherosclerotic molecule, and its activity is decreased in patients with coronary artery disease. Reactive oxygen species have been implicated in the pathogenesis of both endothelial dysfunction and 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 recently demonstrated that iron chelation with desferrioxamine reversed endothelial dysfunction in patients with coronary artery disease (CAD).

In our first study we aimed to determine whether acutely increasing iron would result in oxidative stress in vivo and produce endothelial dysfunction. In healthy controls and patients with CAD we demonstrated that acute iron infusion induces oxidative stress in vivo (increased production of F2-isoprostanes), without affecting nitric oxide-mediated vascular reactivity. Given our previous evidence, this suggests that chronic iron overload is necessary to affect endothelial function, and by inference, atherosclerosis.

In our second study we hypothesised that aortic and coronary trans-lesional ferritin levels, a marker of iron stores, would relate to coronary plaque characteristics on intravascular ultrasound and clinical presentation as stable versus unstable angina. We have demonstrated that markers of iron stores and oxidative stress are increased in coronary atherosclerotic plaque, and are released with plaque disruption. Redox-active iron appears to contribute to higher coronary plaque burden, positive remodelling and unstable presentation.

Prevention of the No-reflow Phenomenon in Myocardial Infarction
Defined angiographically, the "no-reflow" phenomenon manifests as an acute reduction in coronary blood flow in the absence of epicardial vessel obstruction. No-reflow (or slow-flow) occurs in up to 2% of all percutaneous interventions (PCI) and in 30-40% of interventions in acute myocardial infarction (MI) when defined by myocardial perfusion techniques. If persistent, no/slow-reflow may result in MI, or extension of MI, and is associated with a poor prognosis. Verapamil and adenosine are commonly used treatments, however, recent experimental studies and small case-series reports have suggested that sodium nitroprusside (SNP) is an effective alternative therapy for no-reflow. However, few patients reported were being treated for MI. Recent retrospective data presented by us at a national conference suggest that SNP is as effective and safe a treatment for no/slow-reflow as verapamil in the setting of PCI for MI. However, prospective, randomised studies will be required before this therapy can be recommended generally. The aim of our proposed 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.

Grants, fellowships and other funding
NHMRC Project Grant: "A novel mechanism for manipulation of peripheral glucose utilization in patients with type 2 diabetes mellitus"; Kingwell BA, Duffy SJ; 2004-2006; $93,250.00 P.A.

Baker Heart Research Institute Project Grant: 2007 – Chief Investigators: Bronwyn A. Kingwell, Assam El-Osta, Mark Febbraio & Stephen J. Duffy; "Does a high fat diet initiate an epigenetic program for diabetes?"; $150,000 per year for 3 years

Bio
Dr Peter Kistler

Dr Peter Kistler has been newly appointed as the Head of Clinical Electrophysiology Research at The Baker Heart Research Institute and consultant cardiologist/electrophysiologist at The Alfred Hospital and The Royal Melbourne Hospital. He is presently supported by the Neil Hamilton Fairley fellowship provided by the NHMRC and National Heart Foundation. He was recently awarded the inaugural CSANZ/14th world congress of cardiology research investigatorship.

Following physician training at The Royal Melbourne Hospital he completed a PhD in electrical and structural remodeling associated with atrial arrhythmias under Professor Jonathan Kalman. This was supported by a postgraduate research scholarship from the NHMRC. This work has been recognised nationally and internationally by selection as a finalist for the Young Investigator Award Competition of the North American Society of Pacing and Electrophysiology and the Heart Rhythm Society 2004. This is the leading international prize for young researchers in cardiac arrhythmias. His work describing the atrial changes in an ovine model of hypertension won selection in the Ralph Reader Basic Science Award at the Australasian Cardiac Society 2005. He was awarded the Heart Rhythm Society Fellow Clinical Research Award in the USA in 2005 for insights into P-wave morphology.

He completed postdoctoral studies on new mapping technologies and ablation strategies for atrial fibrillation at St Bartholomews Hospital in London, UK. He has 41 publications on a broad range of electrophysiological and pacing topics with 24 first author publications including leading international journals such as Circulation, The Journal of the American College of Cardiology and European Heart Journal.

He has made invited presentations at European cardiac arrhythmia society (ECAS) meeting in 2007, European Live Atrial Fibrillation course, United Kingdom 2005 and Australasian cardiac society meeting (CSANZ) in 2006. He has made oral abstract presentations nationally (CSANZ 2005/6) and internationally (Heart Rhythm Society USA 2004/5/6 and ECAS 2005/6). He is an invited reviewer for international journals: Journal of the American College of Cardiology (JACC), Heart Rhythm Journal, Pacing and Clinical Electrophysiology (PACE) and Journal of Cardiovascular electrophysiology (JCE).

He has established an arrhythmia clinic at The Alfred Hospital with Dr Archer Broughton. He is particularly interested in mapping and ablation of complex atrial arrhythmias including atrial fibrillation. He has extensive experience in device management including cardiac resynchronisation and defibrillator therapies. His research will focus on improving our understanding of the mechanisms responsible for the "emerging epidemic" of atrial fibrillation and ablation strategies to improve the success of catheter ablation.

OTHER PRIZES INCLUDE

Tony White won the Clinical Young Investigator Award at the World Congress of Cardiology in Barcelone in September 2006. (Matrix metalloproteinase-3 genotype is associated with higher coronary plaque burden, positive remodeling and increased risk of unstable disease. AJ White, S.J. Duffy, AS Walton, S. Mukherjee, JA Shaw, GL Jennings, AM Dart, BA Kingwell)

Our study showing that ramipril improves walking ability in patients with peripheral arterial disease was named the top Australian clinical publication for 2006 by CSANZ: (Ahimastos AA, Lawler A, Reid CM, Blombery PA, Kingwell BA. Ramipril markedly improves walking ability in patients with peripheral arterial disease. Annals Int Med 144: 660-664, 2006. Impact factor 13.25)

COACH Program: Winner of the 2006 Australian Healthcare Association Baxter Healthcare National Innovation Award

Category 1: Health Outcomes: The COACH Program: an evidence based, telephone delivered, disease management program proven to reduce hospital utilisation in patients with coronary heart disease. Awarded at AHA National Congress, Brisbane, November 9, 2006.

PhD Students
Ahimastos A (PhD)
Anderson J (PhD)
Ballinger M (PhD)
Bertovic D (PhD) - BK
Connelly N (PhD)
Dawood T (PhD)
Drew B (PhD)
Henstridge D (PhD)
Huynh N (PhD)
Iles L (PhD)
Khong S (Hons)
Mariani J (PhD)
Mukherjee S (PhD)
Murphy A (PhD)
Nair R (PhD)
Ng JF
Rose, H (PhD)
Toh A (Hons)
Vaddadi G (PhD)
White A (PhD)

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