Research into amyloidosis

Amyloidosis is a serious condition that can lead to problems with the heart and other organs. Now BHF research is discovering that it might be more common than previously thought, as Sarah Brealey explains.

Image of Dr Paul Scully

Dr Paul Scully is part of a team using heart scans to spot amyloidosis.

Amyloidosis and heart valve disease

Heart valve disease is a common problem, especially as we get older. The result can be symptoms of heart failure, such as breathlessness and tiredness, and it can lead to the need for surgery or another procedure to replace the valve. The most common form of the disease, aortic stenosis, affects around three in every 100 people over the age of 75.

But what if some of these people have a completely different problem? New research we’re supporting suggests that amyloidosis, a condition always thought to be rare, could be responsible. So what is this mysterious condition?

I’m really grateful to the BHF for taking the risk and funding this

Professor James Moon

Our cells are built from proteins, and those proteins are made of long chains of amino acids. They become three-dimensional through a process called protein folding. This folding is controlled by your genes and has been described as “the final step in the decoding of genetic information”.

Protein folding is vital to how our bodies work – the end result must be the right three-dimensional structure, or the cell won’t work properly.

Usually, protein folding happens automatically – all the information needed to control it is contained within the protein itself. In amyloidosis this goes wrong, and proteins that don’t fold correctly clump together and form deposits in the tissues of your body, including the heart. Over time, this damages the tissues.

Amyloidosis also contributes to other diseases – the most familiar is Alzheimer’s disease, where amyloid deposits build up in the brain.

Surprisingly common


Image of Dr Paul Scully and Professor James Moon

BHF-funded research is a collaboration between Dr Paul Scully, left, who deals directly with patients and Professor James Moon, right, heading up the lab work.

Now, the latest BHF-funded research suggests that a significant number of people with severe narrowing (stenosis) of the aortic valve may have a type of cardiac amyloidosis called transthyretin amyloidosis (ATTR). This research is being carried out at University College London by Professor James Moon, Dr Paul Scully and colleagues.

Professor Moon says: “We couldn’t have done any of this without the BHF. The latest grant was quite risky, we were challenging established beliefs and it wasn’t guaranteed that we would find anything, so I’m really grateful to the BHF for taking the risk and funding this. “Although it has always been thought to be rare, we now know that ATTR cardiac amyloidosis is not rare if you start looking for it in the elderly. “Amyloidosis is quite a severe disease, so it is important to make sure we are getting the diagnosis right and treating it appropriately.”

A future direction of our research could be to investigate new cardiac amyloidosis treatment for these patients, and how the outcomes compare to TAVI

Dr Paul Scully

People who need a new aortic valve have it replaced either through open heart surgery or through transcatheter aortic valve implantation (TAVI), a less invasive procedure usually used for older, more frail patients. Professor Moon and colleagues have been studying both these groups at Barts Heart Centre in London.

They recently published a study of TAVI patients aged 75 and older – and found that one in seven have amyloid deposits in their hearts.

A previous study followed a slightly less elderly group of patients having aortic valve replacement surgery, and found a significant minority had undiagnosed amyloidosis (six per cent of those over 65 with the most common type of aortic stenosis). Just as importantly, both studies suggest that patients with cardiac amyloidosis do worse following their valve replacements than those without.

“That suggests the conditions are related and may somehow be interacting,” says Professor Moon. “In some cases the stenosis might only be moderate, but the amyloidosis is making the symptoms worse.”

Dr Paul Scully, whose work is funded by the BHF, says: “The patients in the research who are found to have cardiac amyloidosis are offered the opportunity to see the specialists at the National Amyloidosis Centre, who identify what type of amyloidosis they are likely to have and any implications for their ongoing care.

“Ultimately the question is: should patients found to have both aortic stenosis and cardiac amyloidosis still undergo a TAVI procedure? The study we have done is relatively small, but will form the basis for larger studies, which we are setting up now.

“A future direction of our research could be to investigate new cardiac amyloidosis treatment for these patients, and how the outcomes compare to TAVI.”

Harold Rubin, 91, from London, took part in the research and was found not to have amyloidosis. “Taking part in the research wasn’t any difficulty for me, it was just a case of having an extra scan,” he says. “I am pleased that it will benefit other people. I am really grateful that I had this treatment [valve replacement] at my age.”

The next step is to expand the research to more hospitals and larger numbers of people. There is also potential to look at whether amyloidosis is involved in other causes of heart failure, such as hypertrophic cardiomyopathy.

“At the moment we are not identifying the vast majority of amyloidosis patients,” Professor Moon says. “We could get them early and offer better treatment. Some people may say this condition is a normal part of ageing – but I don’t buy that. Why shouldn’t we live in better health in old age?”

More useful information