For decades, Australians born with half a heart were told not to exercise because it could cause a strain on the muscle and even sudden death.

But a world-first Heart Research Institute study is looking at whether exercise is actually the key to improving quality of life for people with single-ventricle congenital heart disease.

More Australians adults are living with the condition because of healthcare advancements but are mostly inactive because of the current health advice, says Associate Professor Rachael Cordina.

"Restricting physical activity has actually been very unhelpful, both on physical health and on mental health and sense of wellbeing," Dr Cordina, who is the study's lead researcher, told AAP.

"As we've gotten more experience and more scientific evidence, we've realised that actually exercise is very beneficial and not actually harmful when it's done in the right way."

The study, which will begin in June, will follow about 400 participants aged 10-55 as they complete intensive resistance training over four months.

The group will then be monitored for a further eight months as they continue training sessions independently at home.

A preliminary study showed there were benefits to exercise but this new Australian trial will provide more complete answers, Dr Cordina says.

"There's still a culture of fear among some doctors and family about exercising, so it's important we address those fears with proper science," she said.

"We've been able to leverage $5 million to run a proper trial ... to help us develop a proper model of care that we can roll out for all the people living with these kinds of heart abnormalities."

People with congenital heart disease who live in Western Australia, Queensland, NSW and Victoria will be eligible to participate in the study.