Document Sample
					Superficial femoral artery
      (SFA) atherectomy                SFA prior to treatment   SFA after atherectomy   The plaque excised from the artery.
            and stenting.              – note blockage.         and stenting.

                                                                                                                • Triple R study: this study involves the evaluation

                                      The Department of Cardiovascular Medicine (Heart
                                      Centre) continues to undertake research ranging from                           of patients who require resynchronisation therapy
                                      studies into the basic mechanisms of disease through                           for poor left ventricular function with a left bundle
                                      to evaluation of clinical practice under the overall                           branch block. These patients are evaluated with a
                                      direction of Professor Anthony Dart. The majority of                           cardiac MRI and an echocardiography and Doppler
                                      studies reported have been performed in collaboration                          study prior to insertion of a biventricular pacemaker.
                                      with a number of colleagues, both within and outside                           The benefits of therapy are further assessed post
                                                                                                                     procedure using echocardiography.
                                      the department.
                                                                                                                •    Study on left ventricular strain and diastology
                                                                                                                     in cardiac transplantation patients: cardiac
                                      Several developments during the year have                                      transplantation patients are assessed using
                                      considerably strengthened the research capability                              echocardiography including tissue Doppler, strain
                                      of the department. Notable among these have been                               and strain rate imaging to better evaluate diastolic
                                      considerable work in relation to peripheral vascular                           function.
                                      disease and expansion of our clinical and research                        •    Patent foramen ovale closure with a percutaneous
                                      program in cardiac MRI.                                                        device in patients with unexplained cerebral
                                                                                                                     vascular events from other causes: these patients
                                      Recruitment of new staff has given the department                              have an Amplatzer patent foramen ovale closure
                                      the opportunity to initiate and extend research                                device placed in the cardiac catheter laboratory
                                                                                                                     under radiological and echocardiography guidance.
                                      into atrial fibrillation, an increasing clinical problem.
                                                                                                                     The adequate positioning of the device and
                                      The acquisition of new catheter laboratories with
                                                                                                                     successful closure of the patent foramen ovale are
                                      electrophysiological capability has been a crucial step                        then assessed by echocardiography.
                                      in allowing the development of a research interest in                     •    Assessment of diastolic function and vessel
                                      this area. As part of this, we have recruited Dr Peter                         compliance in diabetes: this study involves the use
                                      Kistler (see profile) to develop clinical electrophysiology                     of echocardiography to assess diastolic function
                                      research.                                                                      in patients with Type 1 and Type 2 diabetes and a
                                                                                                                     normal control group.
                                      Similarly, the upgrading of echocardiographic
                                      equipment has made it feasible for the department to                      The Heart Centre has also been involved in performing
                                      plan for a range of studies not previously possible.                      echocardiograms in the following studies which have
                                                                                                                been performed by other departments:
                                                                                                                • Morbid obesity study: morbid obese subjects
                                                                                                                  are being evaluated for cardiac function and
                                      NONINVASIVE CARDIAC SERVICES                                                cardiovascular risk profiles following substantial
                                      (Dr Jack Federman)                                                          weight loss. They are having a full echocardiogram
                                      The Heart Centre has had major involvement in the                           and studies of the intimal / medial thickness of their
                                      following research studies during 2006:                                     carotid vessels.
                                      • Veritas study: this study involves the placement                        • Ideal study: this study involves the assessment of
                                          of a percutaneous mitral annular clip device to                         left ventricular function by echocardiography to try to
                                          reduce mitral regurgitation in patients with poor left                  determine the optimum time to commence dialysis
                                          ventricular function. Echocardiograms are performed                     in patients with chronic renal failure.
                                          before the procedure to select suitable patients                      • Coenzyme Q10 study: this study involves the use of
                                          and quantify the degree of mitral regurgitation,                        echocardiography to assess the changes in cardiac
                                          with echocardiography studies being performed                           function in heart failure patients given treatment with
                                          during the procedure to assess the response to                          coenzyme Q10.
                                          various degrees of tension on the mitral annular                      • Ultrafine study: this study involves the use of
                                          device. Follow up echocardiography studies are                          echocardiography to assess the cardiac effects of
                                          then performed to assess the subsequent benefits                         ultrafine particles in the air. There is also a respiratory
                                          of the device with regard to the degree of mitral                       assessment of these patients.
                                          regurgitation and left ventricular function.

• Homeostasis study: this study uses echocardiography to              CLINICAL PHYSIOLOGY
   assess cardiac function in patients with severe heart failure
                                                                      (Associate Professor Bronwyn Kingwell)
   who have guided home self therapy.
                                                                      Perindopril reduces large artery stiffness and aortic root
Other studies in which the Heart Centre has been involved             diameter in patients with Marfan syndrome.
include:                                                              Aortic stiffness is elevated in Marfan syndrome (MFS) and
• Bone marrow transplant study: these patients having bone            contributes to aortic dilatation and rupture, the major cause of
   marrow transplantation are having regular exercise stress          premature death in this population. Given the known beneficial
   tests to assess exercise capacity.                                 effects of angiotensin converting enzyme inhibitors (ACEIs)
• BNP trial: this study involves an assessment of the serum           on arterial stiffness, the effect of perindopril therapy on aortic
   BNP levels in patients presenting to the Emergency                 stiffness and aortic dilatation in MFS patients was examined.
   Department with symptoms of shortness of breath. Clinical          MFS patients on standard β-blocker therapy were randomised
   data are reviewed following hospital discharge to ascertain
                                                                      to also receive either perindopril or placebo for 24 weeks in
   whether the patient had evidence of heart failure at the time
                                                                      a randomised, double blind study. Perindopril reduced both
   of presentation.
                                                                      arterial stiffness and aortic root diameter. While perindopril
                                                                      marginally reduced mean blood pressure, importantly, the
International Collaborative Trials
                                                                      observed changes in both stiffness and aortic diameter
FREEDOM: this study evaluates patients with diabetes mellitus
                                                                      remained significant when mean blood pressure was included
who have multivessel coronary artery disease and compares
                                                                      as a covariate. Thus ACEIs reduce aortic stiffness and aortic
coronary artery bypass surgery with insertion of drug eluting
                                                                      root diameter in MFS patients and may potentially protect
stents in the diseased arteries. The current recommended
                                                                      against aortic rupture.
therapy for such patients is coronary artery bypass surgery.
The use of multiple drug eluting stents has not been studied
                                                                      Novel activators of AMP-kinase as potential therapies for Type
specifically in diabetic patients with multivessel coronary artery
                                                                      2 diabetes
disease. The study involves 2,400 research participants in
                                                                      AMP-activated protein kinase (AMPK) is a key metabolic
medical centres in the US, Canada, Europe, South America,
                                                                      enzyme, responding to low levels of energy by increasing
Australia and New Zealand.
                                                                      energy production via increased glucose uptake and
                                                                      fatty acid β-oxidation. Therefore, activators of AMPK are
RE-LY: this study is evaluating patients with uncomplicated atrial
                                                                      potential candidates for the therapy of Type 2 diabetes. New
fibrillation, comparing warfarin and a direct thrombin antagonist.
                                                                      mechanisms of AMPK activation were examined using two
This will potentially achieve the same benefit as warfarin but
                                                                      novel compounds in human primary skeletal muscle cell
at a fixed dose and without the need for regular blood tests to
monitor INR.
                                                                      Vastus lateralis muscle biopsies were obtained from healthy
ILLUMINATE: this trial was testing a new drug (Torceptrapib)
                                                                      male controls and males with Type 2 diabetes. Two novel
that increases HDL cholesterol (good cholesterol) in patients
                                                                      agents stimulated glucose uptake and fat oxidation in primary
with diabetes or coronary artery disease. The trial was
                                                                      human skeletal muscle cultures obtained from biopsy through
terminated early on advice from the study’s Data Safety
                                                                      direct activation of AMPK. Glucose uptake was increased
Monitoring Board due to excess mortality in the
                                                                      relative to basal glucose uptake for the respective cell types in
treatment arm.
                                                                      both healthy and Type 2 diabetes cells. These responses were
                                                                      equivalent to that observed with a pharmacological dose of
BEAUTIFUL: this trial will examine the effects of ivabradine
                                                                      insulin. Bak02 induced glucose uptake only in Type 2 diabetes
in patients with coronary artery disease and impaired heart
                                                                      cells. These data clearly demonstrate that both new agents
function. Ivabradine decreases heart rate and has been shown
                                                                      activate AMPK to increase glucose uptake and fatty acid
to decrease the frequency of chest pain and allow patients to
                                                                      oxidation in human primary skeletal muscle cell culture.
exercise for longer periods of time. The purpose of the study is to
evaluate whether ivabradine reduces cardiovascular events when
                                                                      Matrix metalloproteinase-3 genotype is associated with higher
given in addition to usual treatment for heart disease.
                                                                      coronary plaque burden, positive remodelling and increased
                                                                      risk of unstable disease
SHINE: this study is evaluating the dose effect of a new
                                                                      The matrix metalloproteinases (MMPs) are enzymes responsible
anticoagulant drug in patients who are hospitalised with angina
                                                                      for modulating the protein scafffolding between cells, and
or a heart attack and are scheduled for an angioplasty.
                                                                      are plausible candidates for susceptibility to acute coronary
                                                                      syndrome. The possibility that common MMP polymorphisms
CHAMPION: this study, sponsored by the Medicines
                                                                      would relate to corresponding MMP plasma levels, coronary
Company, investigates the short-acting, intravenous anti-
                                                                      plaque characteristics and unstable clinical presentation was
platelet agent cangrelor versus high-dose oral clopidogrel in
                                                                      examined. Patients with de novo presentation of coronary
patients with coronary artery disease undergoing percutaneous
                                                                      artery disease undergoing coronary angiography were classified
coronary revascularisation.
                                                                      into unstable coronary syndrome and stable angina pectoris
                                                                      groups using Braunwald criteria.

                                                                      Patients were genotyped for four common MMP promoter
                                                                      polymorphisms. Plaque characteristics were assessed in
                                                                      a subgroup of 40 patients using intravascular ultrasound.

                                                                                                   CARDIOVASCULAR MEDICINE
                                                                                                                 THE AMREP           39
                                         Peter Kistler Dr Peter Kistler has recently been appointed to initiate a clinical electrophysiology
                                         research program at the Baker Heart Research Institute. He is also a consultant cardiologist /
                                         electrophysiologist at The Alfred and Royal Melbourne hospitals. Dr Kistler is presently supported
                                         by an NHMRC / NHF Neil Hamilton Fairley fellowship, and 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 remodelling associated with atrial arrhythmias under Professor Jonathan Kalman. This work
                                         has been recognised by his 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.
                                         His work describing the atrial changes in an ovine model of hypertension won selection in the Ralph
                                         Reader Basic Science Award at the CSANZ in 2005, and he was awarded the US Heart Rhythm
                                         Society Clinical Research Award in 2005 for insights into P-wave morphology.

The 6A allele of the MMP-3 polymorphism was associated                 progression of vascular disease before endothelial dysfunction
with unstable clinical presentation. Furthermore, 6A allele            and highlights the influence of endothelial cell type on
carriers had higher plasma MMP-3 concentration, maximum                leukocyte adhesion.
coronary stenosis, plaque area, percentage plaque burden
and remodelling ratio. Other genotypes did not relate to either        CARDIAC MAGNETIC RESONANCE IMAGING
plaque characteristics or clinical presentation. Thus the MMP-3
                                                                       (Dr Andrew Taylor)
6A allele promotes positive coronary remodelling associated
                                                                       Cardiac magnetic resonance imaging (CMR) provides high
with greater plaque burden and increased susceptibility to
                                                                       definition morphological and functional data of the heart, as
unstable coronary syndromes in humans.
                                                                       well as information on tissue composition. The Heart Centre
                                                                       has recently established a clinical and research CMR service
Ramipril reduces large artery stiffness and improves walking
                                                                       in conjunction with the Department of Radiology. Since
ability in patients with peripheral arterial disease: a causal
                                                                       commencement of the service in 2003, over 400 CMR scans
                                                                       have been performed with a high rate of examination
A Framingham substudy has shown that large artery stiffening
                                                                       success (>95%).
may reduce peripheral blood flow through elevation in pulse
pressure which impairs endothelial function and microvascular
                                                                       The CMR service has been involved in a number of international
reactivity. Previous studies from the department showed
                                                                       multicentre studies, including the OnTarget/Transcend
that the ACE inhibitor ramipril reduced arterial stiffness and
                                                                       substudies, and also more recently the ADDUCE study, which
increased maximum walking time by over 200% in patients
                                                                       evaluates the effect of drug therapy on left ventricular mass.
with peripheral arterial disease (PAD). However, it was not clear
                                                                       Smaller in-house studies have utilised CMR across a broad
whether these were related.
                                                                       range of clinical applications, including the evaluation
                                                                       of the suitability of patients with heart failure for cardiac
Forty PAD patients were randomised to ramipril, 10 mg
                                                                       resynchronisation therapy, diagnostic utility in arrhythmogenic
once daily or placebo for 24 weeks in a randomised, double
                                                                       right ventricular dysplasia, the detection of acute rejection in
blind study. Maximum walking time was recorded during
                                                                       heart transplant recipients, changes in cardiac morphology in
a standard treadmill test. Indices of arterial stiffness were
                                                                       obesity with rapid weight loss and CMR-guided left ventricular
assessed. Ramipril increased maximum walking time, and
                                                                       remodelling surgery. Recently, a large study investigating the
reduced arterial stiffness as assessed by systemic arterial
                                                                       non-invasive evaluation of myocardial fibrosis with CMR in heart
compliance compared with placebo. There were moderately
                                                                       failure, as well as its relationship with diastolic dysfunction, has
strong correlations between the pre/post intervention change
                                                                       commenced. The CMR service has attracted two international
in maximum walking time and the change in indices of arterial
                                                                       research fellows, with a local PhD student commencing in
stiffness. Simple modelling suggests that the major site of wave
                                                                       January 2007.
reflection was moved distally by ramipril. In conclusion, these
relationships are likely to be partly accountable by independent
                                                                       A tripartite research agreement exists between The Alfred
effects of ramipril on both the large and small arteries.
                                                                       hospital, Baker Heart Research Institute and General Electric
                                                                       Corporation (USA), enabling access to CMR sequences
VASCULAR PHARMACOLOGY                                                  not yet available for commercial use, as well as enhanced
(Dr Jaye Chin-Dusting)                                                 technical support. In 2006, The Alfred’s clinical CMR service
Endothelial cell type and activation state affects sP-selectin         was awarded a New Technology Grant from the Victorian
mediated adhesion                                                      Department of Human Services for $350,000 pa for two years,
Leukocyte adhesion via P-selectin to an activated endothelium          which will expand available CMR time to approximately 500
is known to participate in both peripheral and coronary                scans per year.
atherosclerosis. The soluble version of P-selectin (sP-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. Our recent
studies demonstrate that sP-selectin may influence the early

Dr Kistler completed postdoctoral studies on new mapping technologies and ablation strategies for atrial fibrillation at St Bartholomew’s
Hospital, London. He has 41 publications on a broad range of electrophysiological and pacing topics with 24 first author publications, many
in leading international journals.

He made invited presentations at the European Cardiac Arrhythmia Society meeting in 2007, European Live Atrial Fibrillation course, UK in
2005 and the CSANZ meeting in 2006. He is an invited reviewer for Journal of the American College of Cardiology, Heart Rhythm Journal,
Pacing and Clinical Electrophysiology and Journal of Cardiovascular Electrophysiology.

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

HUMAN NEUROTRANSMITTERS LABORATORY                                       Depressive Illness and Panic Disorder
                                                                         Ongoing work in depressive illness and panic disorder has
(Professor Murray Esler and Dr Gavin Lambert)
                                                                         produced some interesting and somewhat unexpected results.
Postural Orthostatic Tachycardia Syndrome
                                                                         Contrary to popular belief, it was found that the brain chemical
The Human Neurotransmitters Laboratory has been
                                                                         serotonin is increased in people with panic disorder, with higher
investigating several disorders that impact on heart health.
                                                                         levels being associated with increased severity of the disorder.
Postural orthostatic tachycardia syndrome (POTS) is a
                                                                         Following treatment with a selective serotonin reuptake
condition that has only been recently identified in medical
                                                                         inhibitor (SSRI), a type of antidepressant, brain serotonin levels
literature. The disorder most commonly affects young women,
                                                                         decreased significantly. The effect of SSRIs on the risk of
but older people, including men, can also be afflicted. It is
                                                                         heart disease is also being investigated. In depressive illness,
characterised by fatigue, palpitations, exercise intolerance,
                                                                         factors involved in inflammation were observed to be elevated,
light-headedness, visual blurring, inability to concentrate and
                                                                         increasing the risk of heart attacks. The laboratory is now
episodic fainting. Many of these symptoms are prevalent in
                                                                         examining possible pathways for this observation and how
other disorders, so it is important to realise that one or more
                                                                         SSRIs might modify risk of heart disease in depressive illness.
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              SECONDARY PREVENTION – THE
there are many in addition to POTS, and are a frequent cause             COACH PROGRAM
of visits to the general practitioner.                                   (Sarah Ballis, Cardiac Coach)
                                                                         2007 sees the COACH program in its fifth year of operation
A hallmark of POTS is that during fainting, blood pressure is            at The Alfred. Since the implementation of the program at
maintained, or only falls minimally, while heart rate increases          this site in December 2003, over 600 Alfred patients have
dramatically. The onset of POTS is often abrupt and in about             received coaching to assist them in achieving the National
50% of cases, follows an infection. POTS appears to be                   Heart Foundation of Australia target levels for their biomedical
a manifestation of overactivity of the sympathetic nervous               coronary risk factors as well as to take recommended
system. One of the most effective ways of diagnosing POTS                cardiovascular medications. The COACH program is a
is tilt table testing, which we perform at the Heart Centre. This        telephone-delivered disease management program that works
test involves heart rate monitoring and inserting a catheter into        to reduce risk factors in patients with coronary heart disease
the artery for accurate blood pressure measurement and blood             (CHD) as demonstrated by the highest level of evidence – a
sampling, at different degrees of tilting. Simultaneous recording        multicentre randomised controlled trial.
of muscle sympathetic nerve activity also provides important
diagnostic information. The laboratory has made significant               Since its inception, the COACH program has consistently
progress in obtaining information that will help identify the            shown positive results for patient outcomes. A three year
possible cause of POTS and possible treatment options                    analysis of outcomes from the four Melbourne hospitals
for sufferers.                                                           operating the COACH program as part of conventional
                                                                         care, demonstrated that coached patients made significant
Metabolic Syndrome                                                       improvements in all of their CHD risk factors including total
Findings from the metabolic syndrome study have shown                    cholesterol, LDL cholesterol, blood pressure, smoking
that not only are the different variables of metabolic syndrome          cessation, exercise and medication adherence. Results
detrimental to the heart but that whole body insulin sensitivity         have also shown that coaching in CHD can reduce hospital
is also significantly associated with whole body sympathetic              readmissions and bed days by 16% and 20% respectively.
activity. To expand on some of our novel findings, the
laboratory is investigating the effects of diet and exercise on          In 2006 the Royal Melbourne Hospital site took an innovative
metabolic syndrome variables and how they modify the risk of             and leading role in the expansion of COACH into new disease
heart disease.                                                           areas and in culturally and linguistically diverse communities.
                                                                         Coaches at the Royal Melbourne Hospital have commenced
                                                                         coaching patients with metabolic syndrome and in addition
                                                                         have developed a protocol for the coaching of Greek speaking

                                                                                     ANAESTHESIA AND PERIOPERATIVE MEDICINE
                                                                                                  CARDIOVASCULAR                          41
clients through the use of trained interpreters. The observed          composition in patients undergoing lower limb percutaneous
success in these new areas demonstrates the ability of the             revascularisation for symptom limiting claudication. Patients
COACH program to be moulded to fit any disease state with               scheduled for percutaneous lower limb revascularisation
measurable risk factor outcomes and target levels. Plans               are pretreated with an infusion of HDL. Several days later,
for the expansion into diabetes risk factor management and             peripheral artery angioplasty and atherectomy is performed
chronic obstructive pulmonary disease are under way. It is             yielding tissue for subsequent histological, biochemical and
hoped that in the future The Alfred site will expand the COACH         immunohistochemical analysis. Recent intravenous ultrasound
program into new health areas, which too may prove to reduce           trial data have shown a promising response to this therapy in
hospital admissions and improve patient outcomes.                      coronary arteries so that further elucidation of the effects of
                                                                       such therapy on biochemical change will be of great interest.
(Professor David Kaye)                                                 HUMAN VASCULAR BIOLOGY LABORATORY
The management of patients with severe heart failure is a major        (Dr Stephen J Duffy)
focus of the Heart Centre. The unit acts as the quaternary
                                                                       Melbourne Interventional Group
referral centre, being responsible for the delivery of complex
                                                                       This is a cooperative database of percutaneous
medical, surgical and device-based therapies in partnership
                                                                       revascularisation procedures that includes seven Victorian
with the Cardiothoracic Surgery Department. In conjunction,
                                                                       public hospitals that perform coronary interventions. The
clinicians and scientists at The Alfred, Baker Heart Research
                                                                       ultimate aim is to obtain short- and long-term outcomes of
Institute and Monash Medical School continue to be very
                                                                       coronary interventions for all patients in the state. Currently,
active in research into the pathophysiology of heart failure and
                                                                       more than 5,000 patients have been entered into this
developing new treatments.
                                                                       database, and 30-day and 12-month follow-up is available for
                                                                       more than 4,500 and 2,500 patients at these respective time
Research into novel devices for the treatment of heart failure
                                                                       points. An additional aim is to provide a framework to complete
has progressed well during the year. The trial of the Ventracor
                                                                       interventional / clinical trials.
artificial heart device in patients requiring subsequent heart
transplantation has been completed. A study of a permanent
                                                                       Relationship of Iron Status to Oxidative Stress in vivo, Nitric
percutaneous device for treatment of mitral regurgitation in
                                                                       Oxide Bioactivity and Coronary Artery Disease Activity
heart failure patients has commenced and several patients
                                                                       Patients with high total-body iron levels may be at higher
have been implanted with a novel system for measuring
                                                                       risk for the development of atherosclerosis and coronary
pressure inside the heart as a guide to lung congestion.
                                                                       artery disease (CAD). In animal models of atherosclerosis,
                                                                       iron has been shown to contribute to the progression of
More mechanistic research work has involved investigating
                                                                       disease development. Endothelial-derived nitric oxide is an
the role circulating stem cells play in heart failure patients, how
                                                                       important anti-atherosclerotic molecule, and its activity is
they interact with the heart and identifying the chemical signals
                                                                       decreased in patients with CAD. Reactive oxygen species
that determine their activity. In the area of heart transplantation,
                                                                       have been implicated in the pathogenesis of both endothelial
Dr Angeline Leet has been actively investigating the influence
                                                                       dysfunction and atherosclerosis. Redox-active iron increases
of newer immunosuppressive drugs on clinical outcome. She
                                                                       production of reactive oxygen species (via Fenton chemistry)
has also developed a program of studies on cardiac fibrosis, a
                                                                       and causes lipid peroxidation. F2-isoprostanes are a reliable
particular problem late after transplant.
                                                                       method for assessment of oxidant stress in vivo. We recently
                                                                       demonstrated that iron chelation with desferrioxamine reversed
PERIPHERAL INTERVENTIONAL PROGRAM                                      endothelial dysfunction in patients with CAD.
(Dr James Shaw)
The Alfred Minimally Invasive Vascular Centre (AMVIC) is               The first study aimed to determine whether acutely
a collaboration between the Cardiovascular Medicine and                increasing iron would result in oxidative stress in vivo and
Radiology Departments. This group has a specific interest in            produce endothelial dysfunction. In healthy controls and
the management of non-coronary vascular disease with an                patients with CAD we demonstrated that acute iron infusion
emphasis on novel endovascular therapies.                              induces oxidative stress in vivo (increased production of F2-
                                                                       isoprostanes) without affecting nitric oxide-mediated vascular
Current research projects include examining potential                  reactivity. Given our previous evidence, this suggests that
predictors of blood pressure improvement following renal artery        chronic iron overload is necessary to affect endothelial function,
stenting. Interim analysis has shown an improvement in blood           and by inference, atherosclerosis.
pressure in the patients undergoing renal artery stenting but,
disappointingly, no useful predictors of improvement have been         In the second study, it was hypothesised that aortic and
seen. This is also the main Australian site for the international      coronary trans-lesional ferritin levels, a marker of iron stores,
CORAL trial, which will compare medical therapy with renal             would relate to coronary plaque characteristics on intravascular
artery stenting in patients with renovascular disease. The             ultrasound and clinical presentation as stable versus unstable
endpoints in this study will include progression to renal failure,     angina. It was demonstrated that markers of iron stores and
blood pressure control and all cause mortality.                        oxidative stress are increased in coronary atherosclerotic
                                                                       plaque, and are released with plaque disruption. Redox-active
The other major area of research involves examining the                iron appears to contribute to higher coronary plaque burden,
effects of intravenous HDL on atherosclerotic plaque                   positive remodelling and unstable presentation.

Prevention of the No-reflow Phenomenon in Myocardial                  POSTGRADUATE STUDENTS
                                                                     Ahimastos A. Effects of ACE-inhibition on walking distance
Defined angiographically, the no-reflow phenomenon manifests
                                                                     and endothelial function during exercise in patients with
as an acute reduction in coronary blood flow in the absence of
                                                                     peripheral arterial disease. PhD, Monash University.
epicardial vessel obstruction. No-reflow (or slow-flow) occurs
                                                                     Anderson J. Examining cognitive function in patients with the
in up to 2% of all percutaneous interventions (PCI) and in 30-
                                                                     orthostatic intolerance. DPsych, Monash University.
40% of interventions in acute myocardial infarction (MI) when
defined by myocardial perfusion techniques. If persistent,            Ballinger M. Role of tyrosine kinases in controlling
no/slow-reflow may result in MI, or extension of MI, and is           glycosaminoglycan length of vascular proteoglycans. PhD,
associated with a poor prognosis. Verapamil and adenosine            Monash University.
are commonly used treatments; however, recent experimental           Bertovic D. The arterial biomechanical and hemodynamic
studies and small case-series reports have suggested that            factors contributing to unstable coronary artery disease. PhD,
sodium nitroprusside (SNP) is an effective alternative therapy for   Monash University.
no-reflow. However, few patients reported were being treated          Connelly N. Mechanisms of vascular changes in hepatic
for MI.                                                              cirrhosis. PhD, University of Melbourne.
                                                                     Dawood T. Affective disorders and their association with the
The laboratory presented recent retrospective data at a national     cardiovascular system. PhD, Monash University.
conference that suggested that SNP is as effective and safe          Drew B. The role of HDL and dyslipidaemia in NO mediated
a treatment for no/slow-reflow as verapamil in the setting of         glucose uptake in Type 2 diabetes. PhD, Monash University.
PCI for MI. However, prospective, randomised studies will be
                                                                     Henstridge D. Contraction mediated glucose uptake as a
required before this therapy can be recommended generally.
                                                                     therapeutic target in Type 2 diabetes. PhD, Monash University.
The aim of our proposed prospective, randomised study is to
                                                                     Huynh N. The role of endothelin and nitric oxide in
determine whether the vasodilators SNP and verapamil will
                                                                     hypercholesterolaemia. PhD, Monash University.
improve coronary blood flow, coronary flow reserve and reduce
myocardial infarct size in patients with myocardial infarction.      Iles L. Myocardial fibrosis and heart failure. PhD, Monash
PRIZES                                                               Mariani J. Gene therapy in heart failure. PhD, Monash
Tony White won the Clinical Young Investigator Award at the
World Congress of Cardiology in Barcelona in September               Mukherjee S. Nitric oxide and oxidative stress in human
2006 for “Matrix metalloproteinase-3 genotype is associated          hypertension. PhD, Monash University.
with higher coronary plaque burden, positive remodeling and          Murphy A. The role of C-reactive protein in leukocyte mediated
increased risk of unstable disease” (White AJ, Duffy SJ, Walton      vascular inflammation. PhD, Monash University.
AS, Mukherjee S, Shaw JA, Jennings GL, Dart AM,                      Nair R. Neovascularisation in the pathogenesis of
Kingwell BA).                                                        atherosclerosis. PhD, Monash University.
                                                                     Rose H. Impact of HIV infection and its treatment on
A study showing that ramipril improves walking ability in            cholesterol metabolism. PhD, Monash University.
patients with peripheral arterial disease was named the top          Vaddadi G. Genetic and epigenetic mechanisms of the
Australian clinical publication for 2006 by CSANZ: Ahimastos         disorders of circulatory control which cause postural syncope.
AA, Lawler A, Reid CM, Blombery PA, Kingwell BA. Ramipril            PhD, Monash University.
markedly improves walking ability in patients with peripheral        White A. Large artery stiffness as a risk marker and therapeutic
arterial disease. Ann Intern Med 2006;144:660-664, (impact           target: structural and genetic aspects. PhD, Monash University.
factor 13.25).

COACH program: winner of the 2006 Australian Healthcare
Association Baxter Healthcare National Innovation Award.             71 journal articles
                                                                     3 book chapters
COACH program: awarded Category 1: Health Outcomes
at Australian Healthcare Association National Congress,
Brisbane, November 2006: An evidence based, telephone
delivered, disease management program proven to reduce
hospital utilisation in patients with coronary heart disease.

                                                                                                 CARDIOVASCULAR MEDICINE          43

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