AMREP Research Report 2011

The Department of Cardiovascular Medicine undertakes investigation and treatment of all forms of adult cardiovascular disease. Inpatient services are operationally divided into Cardiology General (CAGE) and Cardiology Heart Failure (CAHF) headed by Drs S Duffy and P Bergin respectively. Investigative services are operationally divided into invasive investigations (catheter lab and related activities) headed by Dr A Broughton and non-invasive services including echocardiography, Cardiac MRI and Cardiac CT headed by Dr A Taylor. In the recent years the Department has developed a strong program in non-coronary percutaneous intervention and this program is headed by Dr A Walton. The department has an active post graduate training program headed by Dr J Shaw.

Research is actively undertaken in all clinical services. There are close research links with BakerIDI as well as other Alfred departments in particular ICU, Radiology and the department of Allergy, Immunology and Respiratory Medicine. Several departmental staff have conjoint appointments with BakerIDI including Prof Dart and Prof Kaye who leads Heart Failure research within the department. Other senior staff with conjoint BakerIDI appointments include: A/Prof Kistler, who heads clinical electrophysiology of research as well as Drs J Hare and J Mariani. In addition there are numerous clinical PhD students and research fellows primarily working within the department.

In addition to the inpatient ward (3CTC), collocated with Cardiothoracic surgery, the department has two fully versatile catheter labs as well a third lab suitable for limited studies. There are five procedural rooms dedicated for research activities including those requiring invasive investigations and measurements. In addition to the five clinical echo suites, a dedicated research echocardiography facility is operated in conjunction with BakerIDI.

In addition to continuing research in traditionally successful areas such as hypertension, hyperlipidaemia and heart failure the department has an increasing research activity in the later stages of other heart disease and in evolving investigative methodologies. Of particular note is an increased activity in structural heart disease research and related activities such as percutaneous renal denervation. Similarly there has been a growth in research into cardiac electrophysiology, particularly atrial fibrillation and its treatment. The cardiac MRI service has continued to develop and establish itself as a leading site in Australia and there is now increased development in coronary CT. Both continue to be fertile grounds for research. In addition there have exciting new developments in investigating new treatment pathways for out of hospital cardiac arrest including the use of early revascularisation and extra corporeal circulatory support in a project in conjunction with ICU. As previously indicated late stage heart failure remains a significant topic of research within the department. Given the static numbers of patients able to receive cardiac transplantation, there is increasing interest in both short and long term further management of these patients. These include assist devices as well as novel interventional procedures. Dr Leet from the Heart Failure service will be leading a research project into ventricular assist devices in such patients. In addition to investigator led research the department participates in numerous sponsored clinical trials. These include primary and secondary prevention of coronary artery disease, treatments of angina, trials of new anticoagulants in stroke prophylaxis and measurements following coronary stenting.

Several investigator led clinical trials conducted within the department were completed in 2011. In one study Dr Chan investigated whether early administration of intravenous desferrioxamine to patients with myocardial infarction would reduce the extent of cardiac damage. The premise for this study was that there is much experimental work implicating reactive oxygen species in causing ischaemia reperfusion damage and that iron chelation would be a potential means to ameliorate this. Dr Chan used cardiac MRI to sensitively and specifically assess the extent of cardiac damage. Whilst treatment was shown to satisfactorily lower iron levels there was no significant impact on final myocardial size. This study involved more than 60 patients with ST elevated infarct all treated within one hour of their arrival. In other studies however Dr Chan did show that MRI changes consistent with fibrosis were evident in the non-infarcted region of the myocardium following a myocardial infarct. These findings are relevant to the process of remodeling of the left ventricle which occurs after myocardial infarction and well of significant implications for appropriate therapy. In other clinical studies Dr Chan showed that the occurrence of myocardial infarction at the time of major vascular surgery could be largely accounted for by haemodynamic changes rather than plaque instability.

The current widespread use of coronary stenting for the treatment of coronary artery disease has lead to the common use of dual antiplatelet (DAPT) therapy for a substantial number of patients. Many of these patients are also prescribed proton pump inhibitors (PPIs) to lessen their chance of gastric irritation and haemorrhage. There has been speculation that the co-administration of PPIs and drugs such as clopidogrel may lead to a lesser antiplatelet effect and therefore have deterious consequences. The clinical trial conducted within the department by Monash BMed Sci student Himavan Fernando, under the principal supervision of Dr Shaw, did indeed show the significant interaction with esomeprazol study. In addition to publication of this study a review of the topic was published by Dr Shaw's team.

Previous work in the department had investigated the role of percutaneous radio frequency ablation of the renal sympathetic system for the control of blood pressure in treatment resistant hypertension. The results from the earlier study were limited to six months follow-up but this is now been extended to two years showing persistence of the previously noted fall in blood pressure. Studies in renal denervation have now been extended to less severe cases and also to examine the possible benefit of such intervention in patients with heart failure.

Other studies in relation to heart failure carried out under the direction of Prof Kaye have investigated the relation between anaemia and heart failure. Whilst it is well recognized that anaemia is associated with the poorer outcome in patients with heart failure Prof Kaye and his team have recently examined the novel hypothesis to iron deficiency may itself play role in the worsening of heart failure directly. Studies to date have demonstrated that patients with heart failure do indeed have reduced levels of iron in the heart. In a series of further studies the team are investigating how iron deficiency is affecting cardiac function. Members of the department actively participate in the Melbourne Interventional Group Registry and have taken a lead in a number of the reports emanating from this group. Recent such data has indicated that poorer outcomes associated with the peri-procedural presence of atrial fibrillation and the use of intra-aortic balloon pumping in this setting.

Acute coronary syndrome is now the most frequent cause for presentation to the cardiac catheter laboratory. It is widely believed that such acute presentations of coronary disease relate from atherosclerotic plaque instability. Such plaques generally contain less collagen and more lipid than more stable plaques. In recent years species of monocyte derived circulating cells (fibrocytes) have been shown to be present in such plaque. In a series of investigations Dr Fang and Prof Dart have investigated whether circulating fibrocytes may play a role in determining plaque instability. Studies completed in 2011 showed that compared with stable coronary disease patients with unstable angina have lower numbers of circulating fibrocytes and less propensity for monocytes to transform in vitro into fibrocytes suggesting this may contribute to the state of instability. In ongoing studies in association with Dr Ellims and Dr Taylor the role of fibrocytes in myocardial fibrosis is also being investigated. Preliminary results also indicate an impact for circulating fibrocytes numbers and function on the present as determined by cardiac MRI.

Research related achievements in 2011 include the following:

  • The award of a NHMRC five year programme grant totaling more than $12 million to a research team with Chief investigators Prof's Kaye, Dart, Esler, Jennings and also including Prof's Chin-Dusting, Kingwell & Sviridov from BakerIDI. This is the third consecutive programme grant awarded for a clinical research team at the Alfred hospital and will commence at the conclusion of the current quinquennium. This is in addition to the extant NHMRC Centre for Research Excellence award made to Prof's Dart, Kaye, Peter, Jennings, Kingwell and Chin-Dusting.
  • A/Prof Peter Kistler was awarded an NHMRC five year practitioner fellowship to enable him to continue his research into clinical electrophysiology particularly in relation to atrial fibrillation.
  • Dr A Taylor was awarded an NHMRC project grant for research in cardiac MRI.
  • Dr J Hare is in receipt of a Cardiac Society of Australian and New Zealand WCC fellowship.
  • Dr William Chan a doctoral student of Prof Dart and Dr's Duffy and Kaye was awarded the Cardiac Society of Australia and New Zealand Ralph Reader prize for clinical research at the annual scientific meeting.
  • Prof Esler was the invited speaker at the 'Inaugural Anniversary Professor and Lecture of The British Hypertension Society' and was elected as Honorary Life Member of the British Hypertension Society.
  • Dr Rahul Sharma won the inaugural Registrar Research prize at the Cardiac Society of Australia and New Zealand Victorian Division.





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