Understanding heart failure

When Dr Sean Lal was 10 years old, his dad developed acute heart failure from a viral infection.

A heart transplant, performed by renowned cardiac surgeon and alumnus Dr Victor Chang (BSc(MedSci) ’61, MBBS ’63), gave his dad a few more years, but it wasn’t enough to save him from a condition some medical experts have called ‘more malignant than cancer’.

Today, Lal is a consultant cardiologist at Royal Prince Alfred (RPA) Hospital and the director of acute heart failure services.

He’s also an academic in the Faculty of Medicine and Health at Sydney, where his lab studies the mechanisms of heart failure at the molecular level.

Working in his lab at the Charles Perkins Centre (CPC), Lal has been looking beyond the usual named causes of heart failure, such as a heart attack, high blood pressure or diabetes, to find it’s more fundamental drivers. The most common cause of heart failure is blocked arteries which creates a particular problem for women.

Only one in three women has the classic heart attack chest pain, instead most experience shortness of breath, nausea, and pain in one or both arms. This means women are often misdiagnosed, with a recent Sydney study finding they are twice as likely not to receive the most appropriate treatment. This could delay their heart failure diagnosis. “My patients ask me all the time why heart failure happened to them. I can’t give them an answer right now, but I’m doing my best to find out,” Lal says.

The condition is incurable, with death a definite possibility. If you were diagnosed with heart failure in the 1970s, your chance of surviving beyond five years was 30%. Today, with new treatments and faster diagnosis, the five-year survival rate is around 60% for the 30 million people worldwide, including half a million Australians, who currently have heart failure.

While treatments have come a long way in the past 30 years, advances lag behind cancer research. Today, heart transplant is still the only treatment for end stage heart failure, but with 60,000 new heart failure cases diagnosed in Australia each year, only about 100 to 200 transplants are performed.

“We urgently need new treatments. I hate seeing families go through what my family went through,” says Lal, who has just recommended his latest patient at RPA be considered for the heart transplant waiting list: a 41-year-old with a young family.

The Sydney Heart Bank - a visionary centre of collaboration and possibility

As they work to slow the progression of heart failure, Lal’s team has access to an extraordinary resource: the largest bank of heart tissue in the world. Located on campus, it has helped give new insights into why heart failure occurs and how it differs in men and women.

The hearts have been donated by patients from St. Vincent’s Hospital who have suffered from all kinds of heart failure that necessitated a heart transplant. Now, for the first time, heart failure samples are being collected from patients undergoing all forms of heart surgery at Royal Prince Alfred Hospital.

There are also healthy hearts of various ages which were not used for heart transplantation for logistical reasons. These healthy hearts allow researchers to compare diseased with non-diseased tissue.

The Heart Bank, of which Lal is now director, was created in 1989 by Sydney Emeritus Professor Cristobal dos Remedios (BSc ’65 PhD(Sci) ’70 DSc ’95) and the aforementioned, Dr Victor Chang. Their visionary idea was to snap freeze hearts at -196°C using liquid nitrogen, preserving the DNA, proteins and enzymes within the heart tissue for future analysis, when advancing technology might make more possible, as it has.

Today, the Sydney Heart Bank, which is completely not-for-profit, shares tissue samples and data to some of the best heart researchers in the world, including those at Harvard, Oxford, Imperial College London and Johns Hopkins.

New findings and discoveries

Lal’s team recently drew on the heart bank to analyse what makes the heart tick at the molecular level. They found changes in many important processes in the heart, including mechanisms that generate energy for the heart, pathways that deal with injury, clotting mechanisms, and processes that maintain structural integrity. 

The team were also surprised to discover that the thyroid hormone, which is present in every organ and is crucial for metabolism, was ‘switched off’ in the hearts of heart failure patients. 

All this has resulted in a much more layered and sophisticated view of how the heart maintains itself.

“We’re really excited about these discoveries. Now we know more about the basic science underlying some of these processes, we can use them to design new therapies that could treat or even prevent heart failure in the future,” Lal said.

From personal motivation, to the next ambitious undertaking

Born in Brisbane to Fijian immigrants, Lal is bursting with drive, and single-minded about curing heart failure.

“When my dad died, it was difficult for my mum to put me through uni. But I knew from the age of 10, when my dad got sick, that I wanted to be a ‘heart doctor’.

“So I applied for an academic scholarship at Sydney and got it. I completed my four degrees here, met my wife here and now I work here. I don’t think I can ever leave,” laughs Lal. Which is just as well because there is still so much for him to do.

Lal and his team are now hoping to embark on the Heart Bank’s most ambitious project to date – analysing the genome and protein profile (proteome) of all 17,000 heart samples. This equates to more than 260 million pieces of data.

It would be the most comprehensive study of human heart failure ever undertaken and will almost certainly lead to world-first discoveries of what causes heart failure and new therapies to treat and cure it.

Written by Elise Webster for the Sydney Alumni Magazine. Photography by Louise M Cooper and Stefanie Zingsheim.