2014 AMREP Research Report

1. Department Details

Name of Department Cardiovascular Medicine
Name of Department Head Professor Anthony M Dart
Title of Department Head Clinical Program Director
Dregrees of Department Head BA DPhil BM BCh FRCP FRACP

 

2. Brief description of Department and main areas of research

The department of Cardiovascular Medicine provides clinical services for all aspects of adult cardiology including mechanical cardiac support as well as cardiac transplantation. All major clinical services of the department have active research programmes. The Heart failure service research is particularly addressing the phenomenon of Heart failure with preserved left ventricular function, the use of novel agents in systolic heart failure and the role of fibrosis. Research in electrophysiology is particularly concerned with atrial fibrillation in both its consequences and best management. The department has a considerable number of research projects in imaging particularly in cardiac MRI with the focus on cardiac fibrosis. Research into coronary disease is concerned with novel risk markers as well as the coronary microcirculation. There is an active program in structural heart disease therapy, particularly in relation to transcatheter treatment of aortic and mitral valve disease. The department contributes extensively to state and national registries of cardiac procedures. There a number of projects in relation to cardiac risk factors particularly hypertension and newer treatments for elevated blood lipid. In addition to investigator led research, the department participates in a large number of multi-centred sponsored trials particularly in relation to lipid disorders, atherosclerosis and the management of acute coronary syndromes. In addition to research primary in the department, there are a number of collaborative studies with other Alfred Health departments and the Institutes on the AMREP campus. A number of studies have been conducted in collaboration with Baker IDI and Burnet Institutes. In addition studies have been undertaken in conjunction with Alfred departments of Gastroenterology, Rheumatology and Infectious Diseases (HIV) as well as with Cardiothoracic Surgery and ICU. Members of the department authored or co-authored more than 45 full publications during the year, including in journals of the American Heart Association, American College of Cardiology and European Society of Cardiology.

3. RESEARCH HIGHLIGHTS AND ACHIEVEMENTS

A) Brief description of major findings or outcomes from research projects conducted during 2014.

Heart Failure Research

Prof Kaye and his colleagues in the Heart failure and Transplant service undertook a series of studies both to investigate the causes and to develop new treatments for patients with heart failure.

Medical therapy for advanced HF: The care of patients with very advanced HF represents a significant challenge. At present, in many patients, there are no further treatments available due to the presence of other complicating factors. In this context, we have developed an oral formulation of a drug (milrinone) that was previously only available intravenously. Early clinical trial experience has been positive, and this research will continue to expand, with planned multicentre trials.

Cardiac fibrosis: Diffuse (interstitial) scarring of the heart is a major feature of many forms of heart failure, contributing to both symptoms and outcomes. The HF research group, in collaboration with the Imaging group, has worked extensively to better understand the causes of fibrosis and the potential targets for therapy. In patients with hypertrophic cardiomyopathy we demonstrated that although extensive fibrosis is present in the heart (by cardiac MRI), the actual rate of turnover of fibrosis is low, suggesting that anti-fibrotic therapies may require long periods of administration to provide benefit.

Mechanical circulatory support research: In some patients with a severe reduction in cardiac function the use of ventricular assist devices (VADs) can be life-saving. The management of patients with long-term VADs can be challenging for a variety of reasons. In an effort to optimize the performance of the VAD for each patient, we have conducted a detailed series of exercise studies with invasive haemodynamic monitoring. For the first time these studies highlight the need to tailor device settings to each patient and particularly in the context of activity.

Invasive Cardiology and Catheter Laboratory Research

The invasive cardiology service was active in a number of research fields.

A/Prof Walton led a number of studies in structural heart disease and transcatheter therapy. Areas of interest include the continuation of investigation into transcatheter aortic valve implantation using the Corevalve and Edwards valve devices with contribution to the Australian Solace study for Edwards. There are several related local sub-studies including assessment of LV pressure volume loops with Prof David Kaye.

A program 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. Renal denervation for refractory hypertension continues in follow-up phase for the Simplicity and Spyral studies.

Dr Shaw has directed a number of studies into the connection between blood levels of vitamin D and coronary artery disease. One study showed a strong relationship between vitamin D levels and the presence and extent of CAD with a lower vitamin D being a major predictor for the extent of CAD. The basis for this led randomised double blind study in patients with a history of CAD and low vitamin D level who either received placebo or vitamin D for 3 months. The main end point of the study was to see if with the addition of vitamin d platelet function was attenuated compared to those who received placebo. The later studies were performed in conjunction with Prof Karl Heinz Peter who, in addition to his clinical role in the department, heads a highly successful programme of platelet research at Baker IDI.

The Department is a leading site in Victoria and, indeed, Australia for cardiovascular device registries. The Alfred was one of the original sites in 2005 for data collection for the Melbourne Interventional Group (MIG) registry, which now has more than 25,000 patient procedures enrolled with detailed follow up available. In the last 18 months this registry has been complemented by the Victorian Cardiac Outcomes Registry (VCOR), a purely quality assurance registry, which was officially launched by the Victorian Minister for Health at the AMREP site in October 2014. Prof Stephen Duffy is a founding member of both of these registries and is on the
Steering Committee for both MIG and VCOR.

Non-Invasive Cardiology

The non-invasive cardiology imaging service headed by A/Prof Taylor, comprises echocardiography (led by Dr Helen Thomson), cardiac MRI and CT coronary  angiography had played an active role in cardiovascular research in 2014. A particular focus continues to be the evaluation of cardiac fibrosis with cardiac MRI and its relationship with cardiac failure and cardiac arrhythmia, with the group forming important local, national and international collaborations across this theme. Using cardiac MRI T1 mapping to quantify diffuse fibrosis, the group demonstrated an important link between diffuse fibrosis and cardiac stiffness, which is likely to be an
important contributor to heart failure with preserved ejection fraction (HFPEF). Several papers also demonstrated the utility of T1 mapping of the ventricle and atria in the prediction of success following pulmonary vein isolation for atrial fibrillation. The non-invasive cardiac imaging group also published important papers
using echocardiography and cardiac CT angiography.

Electrophysiology Research

The electrophysiology service, headed by Prof Peter Kistler, has a particular research interest in the relationship between atrial fibrillation and heart failure and closely collaborates with the cardiac imaging MRI service in examining the role of fibrosis and other structural abnormalities in the genesis of arrhythmias. A large
multicentre international study (MINIMAX) pioneered at the Alfred investigating techniques of catheter ablation in atrial fibrillation is in the process of submission to a major international journal. TIn the last year Dr Alex Mclellan has been nominated for the second year running for the Asia-Pacific Young Investigator award. Dr Sandeep Prabhu, who is completing his second year of a PhD, is the coordinator the CAMERA-MRI study which is a large randomized study assessing the role of cardiac MRI in patients with atrial fibrillation and heart failure in collaboration with A/Prof Andrew Taylor and several centres around Melbourne.

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

  • Chan, Dr William was the recipient of NHMRC Early Career Fellowship award Neil Hamilton Fairley - Clinical Overseas Fellowship commenced 2013. Title: Effect of exenatide on heart muscle injury in the emergency treatment of heart attacks.
  • Dart, Prof Tony was awarded NHMRC Senior Principal Research fellowship.
  • Duffy, Dr Stephen with other CIs: (Bronwyn Kingwell & Andrew Siebel) received NHMRC Project Grant: No. 1065462: 2014-2016 – “HDL Elevation and Glucose Metabolism: A Mechanistic Proof-of-Concept Intervention Trial in Pre-Diabetes”. $490,468.
  • Ellims, Dr Andris won the 2014 BakerIDI Paul Korner medal for outstanding achievement.
  • Iles, Dr Leah has been awarded a NHMRC/National Heart Foundation Early Career Fellowship commencing 2014.
  • Kaye, Prof David was awarded NHMRC Senior Principal Research Fellowship.
  • Kistler, A/Prof Peter was awarded ‘Professorship’ at the Department of Medicine, University of Melbourne.
  • Kistler, Prof Peter was the recipient of NHMRC Practitioner Fellowship.
  • McLellan, Dr Alex is the 2014 Alfred Health Week Research Poster Prize winner of the 'Noel and Imelda Foster' prize for Cardiovascular Research. Project title: “Reverse cardiac remodelling following renal denervation - atrial electrophysiologic and structural changes associated with blood pressure lowering.”
  • McLellan, Dr Alex was the finalist at Asia-Pacific Heart Rhythm Society meeting in Delhi, India 2014. “Reverse cardiac remodelling following renal denervation - atrial electrophysiologic and structural changes associated with blood pressure lowering.”
  • Stub, Dr Dion has been awarded a NHMRC Early Career Fellowship for four years part-time research funding commencing 2015. Project title: Assessment of remote ischemic conditioning on post-cardiac arrest myocardial dysfunction by magnetic resonance imaging, invasive coronary hemodynamic measurements and markers of inflammation.
  • Walton, Dr Tony was awarded an ‘Associate Professorship’ at the Department of Medicine, Monash University.

4.  2014 FEATURED RESEARCH STAFF

Dr Leah IlesDr Leah Iles has been awarded NHMRC/NHF Early Career Fellowship which commenced in 2014.

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