World-first heart transplant technology giving hope to patients

World-first technology pioneered by researchers at the Victor Chang Cardiac Research Institute and St Vincent’s Hospital, Sydney, is allowing surgeons to transplant donor hearts that have stopped beating after death – setting a new global precedent in organ transplant techniques and reducing wait times on heart transplant lists for patients.

Known as ‘Heart in a Box’ this novel technology has seen the number of successful transplants of hearts that have stopped beating after death (called DCD hearts) soar by a quarter at St Vincent’s Hospital, Sydney, since its introduction. New research revealing the technique has been published in the journal Transplantation.

A paradigm shift in organ donation

Before the first DCD heart transplant was performed in 2014, patients relied solely on donor hearts from brain-dead patients whose hearts were still beating at the time of retrieval.

Dr Yashutosh Joshi, St Vincent’s Hospital cardiothoracic registrar and lead author of the paper, said he expects the number of transplants to increase even further after research revealed survival outcomes were just as successful for those who received DCD hearts as those who received hearts from traditional brain-dead donors.

“Previously, donor hearts from a DCD pathway were not able to be used. In the last eight years we have now been able to retrieve these hearts and increase the donor pool which has had a positive impact on our waitlists with more heart transplants being performed than before,” explained Dr Joshi, who is also a recipient of a Heart Foundation PhD Scholarship.

Since 2014, 74 DCD transplants have been performed by the team at St Vincent’s.

Prof Peter Macdonald and Dr Yashutosh Joshi
Prof Peter Macdonald and Dr Yashutosh Joshi

How ‘Heart in a Box’ works

DCD transplants allow hearts to be donated from patients who have died after withdrawal of life support and in whom death is declared only after the heart has stopped beating. This is achieved by using a defined preservation fluid developed in the laboratory and a machine that allows the heart to beat outside the body which allows the organ to be reanimated and assessed.

Professor Peter Macdonald, from the Victor Chang Cardiac Research Institute and senior cardiologist at St Vincent’s Hospital, led the team that pioneered DCD heart transplant surgery.

“Since 2014 our team of scientists and surgeons have worked tirelessly to ensure outcomes are every bit as successful with this new technology. Now that this has been achieved and proved, we expect many more heart transplant teams around the world to embrace this technology,” he said.

“Around the world, there are now hundreds of people who have received DCD hearts. Our discovery has been life-changing and lifesaving for so many patients.”

Professor Peter Macdonald

Initially, it was found that hearts retrieved from DCD donors took a lot longer to recover after transplantation. Around a third of patients had to be placed on a machine similar to heart-lung bypass for a short period of time to allow the newly transplanted heart to recover. However, the team from the Institute and the hospital has since worked out how to better protect DCD hearts during retrieval and transport, drastically reducing the need for this with only a small percentage now requiring temporary bypass.

Going forward, the team is now looking at ways to extend the period of time hearts can survive without circulation prior to transplantation.

Whilst the team at St Vincent’s Hospital in Sydney is the only one in Australia which can perform DCD transplants, its transplant team travels the country to retrieve suitable donor hearts by using the ‘Heart in a Box’ machine.

DCD Heart transplantation is now being carried out in the US, Spain, Belgium, the Netherlands, and the UK, where close to half of all transplants are now with DCD hearts.

Community-led approach reducing rheumatic fever

A community-based research project in the Northern Territory is providing hope to remote communities in reducing rheumatic fever cases and the bacterial infections that trigger the condition.

Rheumatic fever, caused by household crowding and high rates of untreated streptococcal infections in children, can have devastating consequences, such as causing heart disease at a young age.

Community-driven activities key to success

The study – part of a 4-year collaboration with Menzies School of Health Research, Telethon Kids Institute, Sunrise Health Service and NT Health – focused on reducing household health risks through community-based activities led by Aboriginal Community Workers, in a bid to curb infection rates.

Housing and environmental health support – such as fixing showerheads, broken pipes and other health hardware – as well as information-sharing about rheumatic fever and assisting families to navigate healthcare, made up the focus of the activities.

This helped people gain the knowledge needed to seek medical treatment, which initially increased the number of reported infections. Because those infections were then able to be properly treated, rates of infection decreased to below baseline levels, especially in children.

Study co-author and Chairperson of the Board for Sunrise Health Service, Anne-Marie Lee, said the findings suggested the community-led activities translated into a reduction of the types of infection that drive rheumatic fever. The number of new cases of rheumatic fever also decreased during the study.

“Indigenous people working on the ground from that community, it works well. It doesn’t work if an outsider thinks that they can come in. You have to get local people on the ground to do the job,” Ms Lee said.

Director of RHDAustralia and Aboriginal advisor for the study, Ms Vicki Wade, agreed.

“It is so important for rheumatic fever control to be community-led. Rheumatic fever is fuelled by the socio-economic determinants of health, so that’s what we need to tackle, using scientifically based approaches that are co-designed in partnership with communities,” Ms Wade said.

Members of the research team together in Northern Territory, Australia
Members of the research team together in Northern Territory, Australia (L-R): Dr Vicki Kerrigan, Angela Kelly, Anne-Marie Lee, Segora Babui, Professor Anna Ralph, Valerina Mungatopi, Catherine Halkon

First of its kind study in Australia

Study lead and Senior Clinical Research Fellow at Menzies School of Health Research, Professor Anna Ralph, said rheumatic fever had declined in southern parts of Australia and globally in high income countries in the mid-1900s as standards of living improved – otherwise known as primordial prevention.

“Translating the key components of primordial prevention into tropical and central Australia requires innovation and strong partnerships,” Professor Ralph said.

“This is the first time Australian data has been published on the health impacts of community-led rheumatic fever primordial prevention. These findings are promising but need to be scaled up to whole communities.”

The research has been published in the International Journal of Environmental Research and Public Health and funded by the National Health and Medical Research Council, the National Heart Foundation and Bupa Foundation.

Motor neurone disease genetic marker discovery

A genetic variant linked to the most common form of motor neurone disease, which holds potential as a genetic marker to better treat the neurological disease, has been discovered by researchers at the Perron Institute and Murdoch University.

The study represents a step forward in the quest to find new genetic markers to understand and advance new approaches to treat the complexities of motor neurone disease (MND).

MND is a neurodegenerative disease resulting in progressive paralysis. An estimated five to ten percent of cases are familial (hereditary), but most are sporadic.

Study marks first genetic association of its kind in MND research to be published

The collaborative research investigated the Stathmin-2 gene, which is necessary for neuron growth and regeneration. The team uncovered a structural variant within this gene that is linked to sporadic amyotrophic lateral sclerosis (ALS), the most common form of MND.

Results indicate that the variation is a risk factor and may affect the progression of the disease in some patients.

Professor Anthony Akkari, senior author of the study who heads the Motor Neurone Disease Genetics and Therapeutics Research team at the Perron Institute and Centre for Molecular Medicine and Innovative Therapeutics at Murdoch University explained.

“Identifying variations in genetic makeup is a key element in improving approaches to preventing, diagnosing and treating diseases such as MND.

“Overall, in this area of unmet need, the aim is to discover what therapies would work best for specific patient groups. Our research is aimed at filling in genetic pieces of the puzzle.

“As well as giving us a better understanding of disease mechanism, knowledge of this variant could improve outcomes of clinical trials. Grouping participants by this genetic marker would enable researchers to investigate whether the sub-group responds differently to a particular therapy.”

Frankie Theunissen and Prof Anthony Akkari at Perron Institute
Lead researchers Frankie Theunissen and Prof Anthony Akkari at the Perron Institute

Frances Theunissen was lead investigator of the study, a research assistant and PhD candidate at the Perron Institute and Murdoch University.

“This newly discovered genetic variant has the potential to be a disease marker and tool for cohort enrichment in future MND clinical trials and this strategy should become standard practice,” she said.

“It’s a step towards developing new, personalised treatments for motor neurone disease.”

Frances Theunissen

The study was published in the journal Frontiers in Aging Neuroscience.

The collaborative study involved renowned local researchers and international collaborators, including Professors Don Cleveland, John Ravits and Dr Ze’ev Melamed (University of California, San Diego), Professor Richard Bedlack (Duke University, North Carolina) and Professor Alan Mackay Sim (Griffith University, Queensland).

The research was made possible thanks to funding from the Perron Institute, the Giumelli Foundation, Ian Potter Foundation, Racing for MNDi Foundation and the Pierce Armstrong Foundation.

Undercovering link between cardiovascular disease and sleep apnoea

With an increasing number of people losing their lives to heart disease each year, researchers from the Kolling Institute have launched a first of its kind study using MRI technology to broaden scientific understanding of the link between cardiovascular disease and sleep apnoea.

The new study follows latest figures showing cardiovascular disease is the leading cause of death worldwide, killing one Australian every 12 minutes.

This makes the research important and timely, especially given that obstructive sleep apnoea is also increasing and now affects around one billion people. Known as the silent killer, this chronic disease causes low oxygen levels, sleep disturbance and dangerous pressure inside the chest.

Meet the team searching for answers

Royal North Shore Hospital respiratory and sleep medicine specialist Professor Peter Cistulli will lead the study, collaborating with RNSH Head of Respiratory and Sleep Medicine Dr Ben Harris, and Kolling Institute researchers Professor Martin Ugander and Dr Rebecca Kozor, who are experts in cardiac imaging.

The team behind the new study
Meet the team: Nina Sarkissian, Prof Martin Ugander, Prof Peter Cistulli, Dr Ben Harris and Dr Rebecca Kozor

Professor Cistulli said obstructive sleep apnoea has been linked to the development of cardiovascular disease, including hypertension, heart attack, atrial fibrillation and stroke – but there have been no randomised controlled trials confirming a causal link between the two.

“We hope our project will provide definitive evidence of the relationship between sleep apnoea and cardiovascular disease, closing our existing gaps in knowledge and informing future treatment approaches,” he said.

Nina Sarkissian, Director of Research Development for the Sleep Research Group across the Charles Perkins Centre and Royal North Shore Hospital, plays a key role in developing such cross-disciplinary collaborative research programs.

She said “Our CardioSleep Program will be unique, uniting three major disciplines of cardiology, respiratory and sleep medicine, and radiology to develop a precision medicine approach. This will help define which patients are at greatest risk and require personalised treatment.”

“We would like to see this valuable research program drive a new approach, and one which will dramatically reduce the number of people who lose their lives prematurely with a combination of sleep apnoea and cardiovascular disease.”

Nina Sarkissian

The project has been made possible following funding from the Ramsay Research Grant Program.

Changing the way we treat skin cancer

Researchers at the Illawarra Health and Medical Research Institute are leading a multi-institutional research project to better understand and treat squamous cell carcinoma (SCC) of the skin, one of the most common skin cancers in Australia.

Thanks to three-year funding from the National Health and Medical Research Council, IHMRI’s Senior Professor Marie Ranson and Associate Professor Bruce Ashford, who are leading the project, are investigating molecular changes of the cancer to determine what causes it to spread.

“SCC of the skin is so common amongst Australians, but we still don’t know why some tumours spread to nearby lymph nodes and why others do not,” Senior Professor Ranson said.

“Our aim is to decipher the molecular changes that distinguish those SCCs that are likely to spread so that clinicians can identify and treat these patients early.”

Senior Professor Marie Ranson

A better prognosis, more targeted treatments

The project aims to achieve better prognosis and more targeted treatments for one of Australia’s most common cancers and major healthcare burdens.

Patients with aggressive variants of cutaneous SCC often present late, when the cancer has already spread through lymphatics to nodes in the neck.

“When patients present at such a late stage, we have to treat with both radical surgery and high dose radiotherapy. Even then, the chances of surviving beyond five years are only about 50%,” A/Professor Ashford explained.

“We want to be able to identify whether there are early markers that distinguish whether we can avoid unnecessary surgery, or whether we should use even more aggressive treatment.”

Associate Professor Bruce Ashford

Understanding the genetic landscape

Senior Professor Ranson, A/Professor Ashford and the IHMRI team are unravelling the genetic landscape of SCC through the process of whole genome sequencing. Through this process, researchers can see if there is a signature within these tumours that can help predict which ones will spread.

“If we find a signature, it will enable clinicians to more accurately identify at-risk patients to diagnose and treat metastatic SCC early. We have so far completed whole genome sequencing on 33 patient specimens and are completing RNA sequencing of these tumours,” Senior Professor Ranson explained.

The tumour samples are collected from surgery at both Wollongong Hospital and the Chris O’Brien Lifehouse in Sydney. Whole genome sequencing works by comparing cancer cells to normal cells to check for mutations in the DNA. If researchers can find a common pattern of mutation within the cancers, it will help identify which tumours will spread.

“Over three years we hope to examine between 60 and 80 patient specimens. This grant also helps fund the employment of bioinformaticians to help us understand the complex nature of DNA variation in this deadly disease,” said Senior Professor Ranson.

The project is a collaboration with partners, Associate Professor Ruta Gupta from Royal Prince Alfred Hospital, and Professor Narayanan Gopalakrishna Iyer from the National Cancer Centre in Singapore.

Protecting children receiving chemotherapy from hearing loss

Researchers at Ear Science Institute Australia have developed a novel nano-gel therapy to protect children receiving chemotherapy from hearing loss – a common side effect of the cancer treatment.

The project which involves testing the nano-gel in a new study is led out of Ear Science Institute Australia and supported by funding from the Channel 7 Telethon Trust.

A much-needed preventative approach

Lead researcher, Associate Professor Hani Al-Salami, said about half of children who go through chemotherapy will have some degree of permanent hearing loss due to toxicity of the drugs.

“There is currently no proven prevention or cure for this hearing loss, so this new research will test the effectiveness of a nano-gel that is injected into the ear before chemotherapy to prevent the possible side effect of cancer treatment among children,” Associate Professor Al-Salami explained.

“The nano-gel has been developed in partnership with Curtin University by a group of clinicians, pharmaceutical scientists, ENT (ear, nose and throat) surgeons, cochlea physiologists and synthetic chemists using cutting-edge technologies.

“Human bile extract is put through specialised systems to produce a gel, which is capable of being injected into the human ear. It can potentially protect children from the side effects of chemotherapy, which targets and destroys cancer tissues and can also kill other healthy tissues resulting in problems including hearing loss.”

Associate Professor Hani Al-Salami in the lab
Associate Professor Hani Al-Salami in the lab

Looking forward

Ear Science Institute Australia CEO, Sandra Bellekom, said it was a very exciting time for ear and hearing medical research in Western Australia.

“The Telethon grant will allow Ear Science to further develop an established and proven nano-gel, improving efficacy and making it safer for use in our children,” Ms Bellekom said.

The Channel 7 Telethon Trust’s support of Ear Science Institute Australia also includes funding for the procurement of a newly developed scanning electron microscope for use in the research, which is capable of micro and nano scale visualisation of critical features of the nano-gel.

Blood test measures healthy aging in humans

SAHMRI researchers are the first in the world to develop a ground-breaking new blood test to measure autophagy, the body’s process of recycling unwanted or damaged cells to stay healthy.

The research study, which sheds light on autophagy in humans like never before, has been published in the journal Autophagy.

A peek into biological aging

Dr Tim Sargeant, Neurobiologist at the South Australian Health and Medical Research Institute (SAHMRI), said the effectiveness of autophagy in an individual is the strongest indicator of how well they will age.

“Previous studies have shown that the better autophagy is, the less prone the individual will be to cancer and chronic disease.”

“We think the higher you score on this blood test, the longer you’re likely to live and live well.”

Dr Sargeant

Researchers are confident autophagy holds the key to improving outcomes for those with incurable neurological diseases like dementia by signalling risk factors for the condition earlier.

“If we can learn more about what causes the process of autophagy to stop and start, we can work towards creating life-changing interventions.”

Findings significant in other health fields

Dr Tim Sargeant
Dr Tim Sargeant

The research development is also greatly significant to the future of nutrition and dieting.

It’s widely held that factors such as food and fasting influence autophagy in the body, but science hasn’t been able to prove it in humans, until now. 

“This will lead to us being able to point definitively to what kind of fasting is most effective for people and exactly how much exercise they need to do to increase their autophagy,” explained Dr Sargeant.

“In our view, this is the new frontier of health research and our blood test is really the first step that opens the door to a new world.” 

How the test works

The test involves taking a person’s blood and splitting it into two tubes.

The chemical chloroquine is then added to one of the tubes to stop the autophagy process and by comparing this to the other sample, it’s possible to gage how efficiently autophagy is working.

The test is currently in the early stages of development and requires further investigation into its viability for use with patients.

Researchers are optimistic that autophagy measurement will eventually be included in the standard health check-up, like blood pressure and cholesterol tests.

“Our aim is for the blood test to provide clinicians with a baseline from which to experiment with preventative strategies to increase autophagy in their patients; including everything from lifestyle adjustments to drugs.”

The research was carried out in partnership with collaborators at SAHMRI and the University of Adelaide.

The team are currently undertaking investigations that focus on using the test to measure autophagy in those living with a wide range of diseases, with the aim of understanding how this impacts the disease process.