AMREP Research Report 2012

1.    DEPARTMENT DETAILS

Name of Department CARDIOVASCULAR MEDICINE SERVICES
Name of Department Head ANTHONY M DART
Title of Department Head DIRECTOR CLINICAL PROGRAM
Degrees of Department Head BA DPHIL BM BCH FRCP FRACP

 

2.    BRIEF DESCRIPTION OF DEPARTMENT AND MAIN AREAS OF RESEARCH

The department provides a full range of adult cardiological investigations and treatments with active research in all sub-specialty areas.  In view of the continued growth in clinical procedures and research in structural heart disease Tony Walton was appointed to a new position as Head of the Structural Heart Programme.  In other changes Andrew Taylor has taken on the role of Head of Non Invasive Investigations in the department and in view of their increasing importance both to the clinical and research activities of the department this now includes both cardiac MRI and cardiac CT.  James Shaw has taken on the role of supervision of the trainees within the department in addition to his contribution to the hospitals research ethics committee.  In a further innovation this year the department has established the first specialised clinic in Victoria for patients with Hypertrophic Cardiomyopathy (HCM).  This clinic, headed by Andris Ellims, not only fulfils an important clinical lead but has great potential for integrating our genetic, imaging and clinical research in this area.

The department is fortunate to have close research collaborations with several other Alfred departments as well as AMREP partners.  The long tradition of a close interaction with BakerIDI has continued and a significant proportion of the clinical research undertaken by BakerIDI researchers continues to take place within the department and with many staff having conjoint appointments.  Amongst other important collaborations are those with ICU, particularly in relation to sudden cardiac death, with AIRMED, in relation to pulmonary hypertension and sleep pathophysiology, with Infectious Diseases and the Burnet Institute, particularly in relation to cardiovascular complications of HIV, with the Department of Cardiovascular Surgery and with Chemical Pathology and Emergency Department in relation to biomarkers.

3.    RESEARCH HIGHLIGHTS AND ACHIEVEMENTS

A)    Brief description of major findings or outcomes from research projects conducted during 2012
You may wish to focus on providing a narrative of between three to six interesting research projects, depending on the number of research-active staff in your department and whether outcomes are yet available. You are encouraged to include projects that have resulted or have the potential to be translated into improved clinical outcomes for patients at The Alfred or other hospitals.

Structural Heart Disease
Areas of interest include the continuation of investigation into transcatheter aortic valve implantation using the Corevalve device.  A programme for occlusion of the left atrial appendage commenced using the Coherex device for patients who have atrial fibrillation and are at high risk of stroke who are intolerant of Warfarin.  New procedures for the treatment of refractory diastolic heart failure are being evaluated including the creation of an atrial septal defect to offload the left atrium during absence of heart failure.  Follow-up continues for the PC trial involving closure of the patent foramen ovale in young patients with crypogenic stroke.  

Renal denervation for refractory hypertension continues to be a major area of interest with a large VPACT grant received by the Heart Centre for continuing treatment and research in this patient group.  Newer technology will be evaluated in the coming year.  

Acute Coronary Syndromes
The General Cardiology Unit remains extremely busy with acute coronary syndrome presentations.  Data from the ongoing Melbourne Interventional Group (MIG) registry, which now has 19,000 entered patients and in which The Alfred has participated since 2005, show that 70% of percutaneous coronary interventions (PCI) are in patients with acute coronary syndromes.  The Alfred has also agreed to participate in the newly formed Victorian Cardiac Outcomes Registry (VCOR).  Prof Stephen Duffy is on the Steering Committee for both the MIG and VCOR registries.

The department also continues to participate in important international trials of novel antiplatelet and anticoagulant therapies in stable and unstable coronary artery disease.  Ongoing investigator-initiated studies in patients with coronary artery disease include studies by Dr Shaw and colleagues of vitamin D and its relationship to coronary disease and vascular function.  Other studies by Prof Kaye and Dr Duffy include a novel device that can reduce the amount of X-ray contrast given to patients undergoing PCI, particularly in the setting of acute coronary syndromes.  X-ray contrast can have adverse effects on renal function, with contrast-induced nephropathy (or acute kidney injury) occurring in 10-15% of patients.

Out-of-hospital cardiac arrest (OHCA) is a common lethal health problem.  Over the last decade several clinical trials have highlighted the importance of post-resuscitative care in optimizing survival and neurological recovery.  Recently, there have been significant advances in management including recommendations related to regional systems of care, application of therapeutic hypothermia and the utilization of investigative procedures including emergent coronary angiography, cardiac support devices and other tools which provide prognostic information.  Dr Dion Stub has recently completed his PhD studies in this important area and has published extensively on how better outcomes can be achieved by improved systems of care including a recently published a position paper advocating for ‘cardiac arrest centres’ in Australia, along the lines of trauma centres, to optimise patient outcomes in this extremely ill group of patients.

Non Invasive Imaging
Projects have continued in all the imaging modalities including cardiac MRI, CT coronary angiography and echocardiography.  The department has a particular focus on cardiac MRI and a number of projects have been completed or published in 2012.  Many of these have been concerned with the detection and significance of myocardial fibrosis.  Although atrial fibrillation is primarily an abnormality of the atria, diffuse left ventricular fibrosis was identified in patients with atrial fibrillation (AF), providing new insights into the association between AF and adverse ventricular remodelling.  In other studies it has been demonstrated that following an acute myocardial infarction there are changes not only in the infarcted region but also throughout the rest of the left ventricle, which suggests a new paradigm for adverse cardiac remodelling following AMI.  Fibrosis is known to occur in left ventricular hypertrophy including in patients with ‘primary’ hypertrophic disease such as Hypertrophic (Obstructive) Cardiomyopathy.  Whilst generally thought to represent the consequences of local changes, studies by Prof Dart and Dr Fang have shown that these patients also have abnormalities in circulating while blood cells which may contribute to the fibrotic process.

Obesity/Diabetes/Hypertension
Investigations documenting the importance of the sympathetic nervous system and its role in cardiovascular and cardiometabolic disease continued throughout 2012.  Dr Nora Straznicky demonstrated that baseline sympathetic activity was predictive of successful weight loss in subjects with the metabolic syndrome and continued her investigations examining neuroadrenergic dysfunction along the diabetic continuum.  In related work A/Prof John Dixon outlined the clinical predictors of glycaemia response to gastric bypass surgery in patients with type 2 diabetes.  Additionally, in association with sleep and surgical colleagues on campus, an investigation evaluating surgical versus conventional therapy for weight loss on obstructive sleep apnoea was completed and published in JAMA completed.

Therapeutic studies in relation to the sympathetic nervous system were particularly related to the effects of renal sympathetic denervation and followed on from the pioneering initial studies of Dr Tony Walton, Prof Murray Esler and Prof Henry Krum published in the Lancet.  In a series of further investigations A/Prof Markus Schlaich and others are investigating the physiological consequences of this procedure and its possible role in related diseases such as chronic renal disease and, with A/Prof Peter Kistler, atrial fibrillation.

Vascular Disease
Studies by Prof Kingwell and Dr Blombery in collaboration with other colleagues have shown that treatment with the ACE-I, ramipril, is able to improve the distance able to be walked by patients with narrowing of their peripheral arterial circulation, with the findings published in the Journal of the American Medical Association.  Prof Kaye in collaboration with clinicians at the Royal Melbourne Hospital commenced a world first trial of antibiotic delivery via a novel technique termed isolated limb perfusion for patients with severe limb infection.  This study draws upon the successful development of a regional drug system by Prof Kaye, in collaboration with Osprey Medical which he co-founded.  In other studies the role of lipid abnormalities and alterations in immune activation in the development of carotid artery disease in patients with HIV and the role of inflammation in modifying peripheral vascular properties in patients with rheumatoid arthritis and inflammatory bowel disease have also been  examined.  These studies have been possible through close collaboration with the relevant clinical departments as well as AMREP institutes.

B)    Important research-related achievements by staff members of the Department (e.g. awards, prizes, major grants)

Members of the department continue to hold NHMRC funding with 3 career grade people awards, a programme grant, a CRE and project grants.  Particular congratulations this year to David Kaye who became the departments second NHMRC Senior Principal Research Fellow and to Peter Kistler who was awarded a Practitioner Fellowship.  In addition a number of our more junior researchers were in receipt of peer reviewed scholarships to support their doctoral studies whilst Will Chan and Geoff Lee secured NHMRC Neil Hamilton Fairley fellowships allowing them a period of overseas research training to be followed by a period of supported research within the department.  James Hare was a recipient of a CSANZ/14th WCC Research Investigatorship that allowed him to continue his imaging related studies.  In another great achievement David Kaye was awarded the national Eureka prize for translational research for his developmental work in relation to cardiac devices.  Overall studies conducted within the clinical department resulted in approximately 60 peer reviewed publication in 2012.

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