Home > Cardiovascular
Centenary Institute - Medical Research
Centenary Institute - Medical Research

Concealed cardiomyopathies revealed in cardiac arrest survivors

Centenary Institute researchers have discovered that genetic testing can identify ‘concealed cardiomyopathies’ in nearly a quarter of sudden cardiac arrest (SCA) survivors who seem to have a normal heart.

The findings will mean improved diagnosis rates and personalised care for SCA survivors as well as guide the screening of family members who may have the same underlying genetic condition.

The study, reported in the ‘International Journal of Cardiology’, undertook genetic testing and analysis of clinically-idiopathic SCA survivors (individuals where previous clinical investigations had failed to reveal a diagnosis).

The researchers identified a genetic cause of arrest in 22% of the SCA survivors studied. The majority of these newly identified cases had genetic abnormalities associated with cardiomyopathy.

“Cardiomyopathies are diseases of heart muscle. They can impair the heart’s ability to pump blood around the body, leading to heart failure but can also cause electrical changes which can lead to dangerous heart rhythms,” said lead author of the study, Dr Julia Isbister from the Centenary Institute’s Agnes Ginges Centre for Molecular Cardiology.

“These conditions are usually detected on clinical tests such as ultrasound but our findings show that state-of-the-art genetic testing may be useful in revealing cardiomyopathy before structural abnormalities are evident.”

Dr Isbister says that identifying the reason for a SCA is critical for both patients and their families.

“If the specific disease can be diagnosed we are better able to implement personalised care for the survivor. If we discover that the SCA is genetically-based we can then screen family members for similar issues. Screening of first-degree relatives is an extremely important aspect of caring for SCA families, aiming to reduce the risk of further cardiac arrests in the family,” said Dr Isbister.

Professor Christopher Semsarian AM, Head of the Centenary Institute’s Agnes Ginges Centre for Molecular Cardiology and senior author on the study says that the role of genetic testing in the management of SCA survivors requires reappraisal given the results of the team’s findings.

“Current guidelines recommend only limited genetic testing of SCA survivors when a specific genetic condition is already suspected. Genetic testing is not generally recommended for those survivors classified as clinically ‘unknown’,” he said.

“Our study has shown that advances in genetic testing technology and analysis can improve diagnosis rates by revealing heart defects that were previously hidden. A reassessment of guidelines and increased genetic testing may lead to better outcomes for survivors, their families and overall prevention of sudden cardiac death in the young.”

Publication: “Concealed cardiomyopathy” as a cause of previously unexplained sudden cardiac arrest.

Cardiovascular research excellence recognised

Four scientists from the Centenary Institute have had their world-leading research recognised by being awarded prestigious NSW Cardiovascular Research Capacity Building Grants. The grants will help drive the scientists work focused on improving the health of patients with heart and cardiovascular conditions.

“Cardiovascular disease is a leading cause of death and disability in Australia. We need to continue to accelerate our research efforts in this critical health area to develop new and innovative treatments and to improve the heart health of all Australians,” says Professor Mathew Vadas AO, Executive Director at the Centenary Institute.

“Accordingly, these grants are an excellent outcome, both for our scientists who are operating at the very forefront of their research fields, as well as for the wider community who will ultimately benefit from the life-changing medical research being undertaken,” he says.

Successful Centenary Institute scientists and their research are (pictured top left to right):

Professor Philip Hogg. Centenary Institute (ACRF Centenary Cancer Research Centre) and University of Sydney. Awarded a Cardiovascular Senior Researcher Grant. Redefining protein function in thrombosis: Implications for pro-thrombotic states and anti-thrombotic drug resistance in patients with cardiovascular disease.

Dr Paul Coleman. Centenary Institute (Vascular Biology Program), Heart Research Institute and University of Sydney. Awarded a Cardiovascular Early-Mid Career Researcher Grant. Redox control of VWF processing and activity during thrombotic diseases.

Dr Renjing Liu. Centenary Institute (Vascular Biology Program) and University of Sydney. Awarded a Cardiovascular Early-Mid Career Researcher Grant. Targeting Tet2 as a therapy for vascular calcification.

Dr Yanfei (Jacob) Qi. Centenary Institute (Vascular Biology Program) and University of Sydney. Awarded a Cardiovascular Early-Mid Career Researcher Grant. Targeting blood vessel cells to treat atherosclerosis.

The NSW Cardiovascular Disease Research Capacity Building Program and its grants are a NSW Government initiative aiming to drive discoveries that allow researchers to find ways to better diagnose, treat and prevent cardiovascular disease, improving the health and wellbeing of people living in NSW.

Read the full media release here.

New Centenary Institute laboratory launched

The Centenary Institute has officially launched its newest initiative, ‘The David Richmond Laboratory for Cardiovascular Development: Gene Regulation and Editing’ headed up by Associate Professor Mathias Francois (pictured).

A/Prof Francois and his team will be focused on identifying new and innovative therapeutic approaches targeting vascular disease (any abnormal condition relating to arteries, capillaries, veins and lymphatic vessels). Abnormalities in the growth and development of these vessels are associated with human disorders including cardiovascular illness, solid cancer metastasis and inflammatory diseases.

With many of these diseases and disorders having a genetic cause, the team will be looking to determine the molecular events that direct and influence the construction of the ‘vascular tree’ (the network of blood and lymph vessels throughout the body). The aim will be the identification of molecular targets to which novel therapeutics can be first assessed and then generated.

The main focus of the research program will revolve around the biology of a class of protein known as transcription factors (TFs). These proteins act as molecular switches or as the control panel of the genome to turn on and off genetic pathways which drive vascular development.

Until recently TFs were labelled as “undruggable” but recent technology advances have opened up new research directions to efficiently manipulate these targets pharmacologically. The long term goal is to design new treatments that fine-tune gene expression to improve the management of vascular disorders.

Undertaking a highly strategic methodology to this activity, the new laboratory’s research program will be multi-disciplinary in nature, encompassing developmental biology, disease model systems, complemented by biophysics and genomics approaches.

“I’m extremely excited to be joining such a well-regarded and thriving organisation as the Centenary Institute,” says A/Prof Francois. “The appeal of this institution is in the versatility of the research capabilities provided by such world-class scientists.”

“Working in a new research environment with new colleagues from complementary research fields will mean new ideas and more opportunities to think out of the box. This process is  critical to translate knowledge generated from discovery science to more applied vascular research, which hopefully will lead into meaningful treatments that have the potential to change lives,” he says.

Centenary researchers receive cardiovascular disease grants totalling $2.25m

Three Centenary Institute researchers based in Sydney have been awarded grants totalling $2.25m that will help support the diagnosis, treatment and prevention of cardiovascular disease.

The highly competitive grants, from the first round of the NSW Cardiovascular Disease Research Capacity Building Program, were awarded to Centenary Institute’s Professor Christopher Semsarian (left), Professor Jennifer Gamble and Dr Richard Bagnall (right).

Professor Christopher Semsarian, awarded a ‘Cardiovascular Disease Clinician Scientist Grant’ was happy to receive the funding, noting that the grant would support his research into identifying new genetic causes of inherited heart diseases, including that of sudden cardiac death (SCD) in the young.

“We want to find the underlying molecular mechanisms responsible for these life-threatening heart diseases, to provide answers to families as to why their child died suddenly and how can we help prevent these inherited heart diseases from claiming other family members as well as individuals from across the wider community,” he said.

Professor Jennifer Gamble, who was awarded a ‘Cardiovascular Disease Senior Scientist Grant’ will use her funding to explore molecular changes in endothelial cells as they undergo cellular ageing.

“Endothelial cells line blood vessels and changes in their function and structure can result in leaky blood vessels and a chronic inflammatory state,” said Prof Gamble. “These changes contribute to the initiation and progression of age-associated disease including cardiovascular disease. We need to find out what’s happening with these cells at a deeper level as an essential first step to developing potential new therapeutics.”

Dr Richard Bagnall who also received a ‘Cardiovascular Disease Senior Scientist Grant’, will use the funding to support his molecular biology and bioinformatics work into developing improved genetic testing for inherited heart diseases.

“High volumes of DNA sequencing data can now be generated, but it requires sophisticated software and computers to make sense of all that information,” said Dr Bagnall. “I’ll be undertaking a computational analysis of gene sequencing, followed up by laboratory analysis, so that we can precisely identify specific cardiovascular diseases, aiding future diagnostic and treatment approaches.”

Read the full media release here.

NSW Health Article: Professor Chris Semsarian

Professor Chris Semsarian, Head of Centenary Institute’s ‘Molecular Cardiology Program’ is featured in a NSW Health article. It highlights the advanced work that is being undertaken by researchers to better understand the heart and to treat cardiovascular disease.

Work by Professor Semsarian has shown that sudden cardiac deaths in young people are often due to genetic or inherited defects. His focus is on using genetic information to improve diagnosis, to initiate prevention and treatment strategies early in life and to help improve prognosis.

You can read more about Professor Semsarian, what inspires him as well as activities from other leading cardiologists here: https://www.medicalresearch.nsw.gov.au/scientists-solving-mysteries-of-the-heart/

Prestigious journal role for Centenary Deputy Director

Centenary Institute’s Professor Chris Semsarian, Deputy Director and Head of the Molecular Cardiology Program, has been invited to be the new editor-in-chief of the prestigious science journal ‘Circulation: Genomic and Precision Medicine’.

“I’m excited to take on the editorship of the leading cardiovascular genomics journal in the world, at a time when there are phenomenal advances in genomics and precision medicine approaches,” Prof Semsarian said.

“My vision is for the journal to be the ’go-to‘ journal for the latest, state-of-the-art research studies in the field of cardiovascular genomics and precision medicine, with an expanding readership to encompass more general cardiologists, geneticists and other allied health professionals.”

More information on the appointment can be found here.

Study reveals technology role in over-diagnosis of rare inherited heart disease

A new study led by Centenary’s Professor Chris Semsarian AM and Samantha Barrett-Ross from our Molecular Cardiology Program reveals the critical need for greater understanding into diagnosis of little known inherited heart disease.

In collaboration with Wiser Healthcare, Royal Prince Alfred Hospital and the University of Sydney, the study published today in the highest ranking international cardiovascular journal – European Heart Journal, has shown that the use of advanced imaging equipment is driving a significant increase in the diagnosis of a little known inherited heart disease in adults.

In a comprehensive systematic review of 55 studies of Left Ventricular Non-Compaction (LVNC), a rare form of heart disease, the authors of the study have found that an older heart test, echocardiography (which uses ultrasound) diagnosed the condition in 1% of hospital patients and healthy adults. But using a new cardiac MRI test, 15% of adults were reported to have the condition. In some studies, it was much higher, up to 40%, even in studies of large samples of well people.

Professor Semsarian, Head of Centenary’s Molecular Cardiology Program and a leading cardiologist at Royal Prince Alfred Hospital, says, “Finding evidence of heart disease in up to 40% of well adults raises significant questions. Many of the studies were done on well people with no symptoms or signs of heart disease, yet the cardiac MRI showed these abnormal results at alarming levels. This raises questions about the clinical utility of this particular diagnosis. It raises wider concerns too. For example, how should results from new, very sensitive tests be interpreted?”. The study highlights the impact of new technology on what appears to be massive over-diagnosis of the disease. It also provides new insights and guidance on more consistent and accurate diagnosis of LVNC in adults, to enable a reduction in the number of healthy people undergoing the stress of misdiagnosis, and cost and trauma of unnecessary treatment.

Radio Interview

Listen to the ABC RN Health Report interview with Centenary’s Professor Chris Semsarian AM and Samantha Barrett-Ross from our Molecular Cardiology Program.

Read the full media release.

See the published article in the European Heart Journal.

International Day of Women and Girls in Science

Meet Associate Professor Jodie Ingles

Jodie Ingles wears many hats. She is a cardiac genetic counsellor, an award-winning scientist, a widely-published researcher, an Associate Professor, as well as a wife and a mum.

All this, and she’s only 38 years old!

This International Day of Women and Girls in Science, we recognise Jodie for her brilliant breakthroughs in genetic heart research, and for paving the way for female scientists trying to balance life as a researcher with motherhood.

Growing up

Jodie grew up in a small town in country New South Wales, where at the time, only a handful of her high school cohort would go on to study at university. She wasn’t quite sure what she wanted to do, but she loved the idea of science and medicine. Jodie also read books about Ebola and enjoyed the Jurassic Park book series, which she says went into a lot of detail about mathematic and genetic engineering.

“I used to think there was no way a country girl could make this a career. I never had a career plan. I just followed the path that made me happy, and eventually ended up where I am.”

Jodie admits she didn’t know a lot about women in science growing up, but says she was lucky to grow up in a supportive and encouraging environment at home.

“My dad would always buy me books about how things work. When I was considering studying medicine, he called one of the universities and had them post all their information to us.”

Scientific achievements

Jodie went on to complete a Bachelor of Biomedical Science, a Master of Public Health, a Graduate Diploma in Genetic Counselling and a PhD. Most recently, she was promoted to Associate Professor in the Faculty of Medicine and Health at the University of Sydney.

Since 2003, Jodie has been working at the Centenary Institute in Professor Chris Semsarian’s (AM) Molecular Cardiology Program. Her role involves seeing families in the clinic as a cardiac genetic counsellor and overseeing the return of genetic testing results.

As part of her PhD, Jodie co-established the Australian Genetic Heart Disease Registry in 2008, and in 2015, she became Head of the Clinical Cardiac Genetics group at Centenary.

“I do what I do, because for 15 years, I’ve been lucky to meet so many amazing families in our clinics and I want to find answers for them. We are there for families when they’re at absolute rock bottom, and being able to help them through that is our goal.”

Jodie has been the recipient of many prestigious awards and grants, including:

  • NHMRC Career Development Fellowship, Level 1
  • NSW Cardiovascular Research Network Rising Star Ministerial Award
  • Heart Foundation Future Leader Fellowship
  • NSW Health EMCR Fellowship, Cardiovascular Health
  • Rita and Cornforth Medal for PhD Achievement, University of Sydney
  • Peter Bancroft Prize for Research Work, Sydney Medical School
  • CSANZ Affiliate’s Prize

In 2018, Jodie also delivered the prestigious plenary Janus Lecture at the American National Society of Genetic Counselors (NSGC) annual conference in Atlanta, Georgia (US). The conference was attended by about 2,500 genetic counsellors from all around the world.

Balancing academic life with being a mum

On top of being a highly-successful young scientist, Jodie is also a mum. She had her almost 10-year-old son during her PhD and admits while it can be difficult, having a family means she has to make it work.

“Centenary has a great attitude towards working mums. I’m a total workaholic, so I am sure I would burn out very quickly without being forced to leave the office by 4PM. It’s impossible to stress about a grant or research paper being rejected when you have this amazing little human who wants to tell you about his soccer game.”

Jodie says it can become particularly tricky when she’s required to travel overseas for conferences, which usually happens at least five times a year. She believes it’s important to surround yourself with supportive people, saying she’s particularly grateful for her father-in-law who helps her husband look after her son when she’s away.

Her advice to women who are considering having children but also want to progress their career?

“Just do it. There is never a right time, you just find a way. However, I would add that there is only so much time in a day so if you are looking after small children, then you probably need to be realistic about how much work you can achieve.”

Importance of having a mentor

Jodie is adamant it would be almost impossible to succeed in academia without a mentor, because there is no way of being able to see the big picture, and how the little steps along the way lead to something important later on.

“I was lucky to find a great mentor in Professor Chris Semsarian who was able to help guide me in building a track record that is now competitive in the fellowship and grant schemes. Without being able to attract funding, we have no ability to work towards independence.”

Associate Professor Jodie Ingles, Professor Chris Semsarian, cardiac research, heart research, medical research

And now, Jodie is finding joy in helping to create opportunities for junior staff and students.

“Being able to pull people up with you is so important. It’s the only way I’ve been able to succeed and I intend on creating those opportunities for as many people as I can.”

Gender equity in science

Statistics show that while women make-up more than half of science PhD and early career researchers, they account for just 17 per cent of senior academics in Australian universities and research institutes.[1]

As winner of the Centenary Institute’s 2017 Bank of Queensland Gender Equity Award, Jodie is one of those looking to change those figures.

Jodie believes the tide is already turning, with more public recognition of gender issues in the academic sector. However, she also thinks there is much room for improvement.

“It can be easy to blame any rejection on the fact I am female. I think that wondering how it is impacting on how people perceive me and my applications isn’t overly helpful. I would really like to see how blinding of applications would go, like the NHMRC.”

Jodie was also selected as a mentee in the 2018 Franklin Women’s six-month mentoring program, alongside fellow Centenary researcher Dr Jessamy Tiffen.

Advice to girls looking to pursue a career in science

Jodie offers the same advice to anyone looking to enter the world of science, regardless of their gender.

“Science is a career for people who are curious, hard-working, creative and determined. Applying those skills in medical research offers the potential to have a positive impact on many people.”

Looking back on her own career to date, she also believes it’s crucial to be confident in what you do.

“I wish I had believed more in myself. I haven’t had a typical career path and at some level, I still feel like the country girl who needs to always prove herself. That can be exhausting! I’m trying to better accept those insecurities as who I am, but I think it’s important they don’t hold you back.”

About International Day of Women and Girls in Science

  • International Day of Women and Girls in Science is held on 11 February every year.
  • It came out of a resolution adopted by the United Nations General Assembly in December 2015, which established an annual International Day to recognise the critical role women and girls play in science and technology communities.
  • The Day is designed to raise awareness about the significant gender gap which has persisted in all levels of science, technology, engineering and mathematics. Women remain underrepresented in these fields.

Read the media release as a PDF.

To arrange an interview with Associate Professor Jodie Ingles or to request images, please contact: Centenary Institute Media and Communications Manager, Laura Parr, l.parr@centenary.org.au, 02 9565 6108

[1] Gender Equity, Australian Academy of Sciencehttps://www.science.org.au/supporting-science/gender-equity

New insights into why young people die suddenly

A study led by scientists at the Centenary Institute could provide some families with a clearer insight into why a young loved one may have experienced an otherwise unexplained cardiac arrest and in some cases, sudden death.

Arrhythmic right ventricular cardiomyopathy (ARVC) is a poorly understood genetic cardiomyopathy. It occurs if the muscle tissue in the right side of the heart undergoes cell death and is replaced with fat and scar tissue; disrupting the heart’s electrical signals and causing an abnormal heart rhythm.

Researchers from the Centenary Institute, Royal Prince Alfred Hospital, Royal North Shore Hospital and the University of Sydney examined four families in which one family member (under the age of 30 years) had ARVC and experienced a cardiac arrest as a result. In two cases, the patients survived, while in the other two cases, the patients died suddenly.

Studies to date suggest patients must exhibit an obvious structural change to their heart before they are at risk of a sudden cardiac episode. This study shows for the first time that this isn’t always the case, with none of the four patients’ hearts exhibiting any structural changes. In all four cases however, a genetic error in a particular gene called PKP2 was identified.

“This study could force us to re-evaluate how we treat patients with this particular type of cardiomyopathy. For example, should we be more aggressive in treating these patients who carry the PKP2 gene error, but don’t show any clinical evidence of having this disease?” says Head of Centenary’s Molecular Cardiology Program, Professor Chris Semsarian AM.

“It also opens the door for potential gene-targeted therapy further down the track, with the aim of preventing patients with ARVC from experiencing a cardiac arrest.”

Lead author and Head of Centenary’s Clinical Cardiac Genetics Group within the Molecular Cardiology Program, Dr Jodie Ingles says the results may also help to provide closure for some families.

“In many cases of cardiac arrest or sudden death, it can be difficult to identify the precise cause, particularly if the patient’s heart does not show any structural changes. Now, we can attribute a specific gene as to why some people die suddenly, in cases that would otherwise go unexplained,” says Dr Ingles.

View the full media release as a PDF.

Read the paper published in Circulation: Genomic and Precision Medicine.

Learn more about Centenary’s other life-saving medical research breakthroughs.

Inflammation Fact Sheet

Think you know about inflammation? Think again. Redness, swelling, muscle aches…that’s not even the half of it. Chronic inflammation is a key driver of diseases, such as cancer, cardiovascular disease and autoimmune diseases. Read more.