How research is helping to treat hypertrophic cardiomyopathy

Every year in the UK, hundreds of people die without warning because they have an undiagnosed heart condition called hypertrophic cardiomyopathy (HCM). It is the most common cause of sudden cardiac death in under-35s, but thanks to BHF funded research, it is possible to diagnose it and even prevent sudden death, as Sarah Brealey explains.

HCM is a silent killer. It causes thickening of the heart muscle, but in many cases those affected don’t have any symptoms. It can also cause abnormal heart rhythms; these can be fatal. It is relatively common, affecting about one in 500 people – that’s 120,000 people in the UK.

Frost family at a cricket match, Sir David Frost not pictured

One victim of HCM was Miles Frost, the son of broadcaster Sir David Frost. Miles, who ran an investment company, died in July 2015, at the age of 31. He was fit and active, a keen skier and tennis player. On the morning of his death, he did a boxing workout and then went for a run. He was found near the family home by his brother George, who went looking for him when he failed to come back for Sunday lunch.

HCM was first described at a London hospital in the 1950s. Back then it was poorly understood, and for many heart muscle that couldn’t be explained. Thanks to research, much of it funded by the BHF, we now understand the condition much better.

Profile shot of the late Mile Frost with arms crossed

 

We know that it runs in families and how it is inherited. If someone has HCM, each of their children has a 50-50 chance of inheriting the faulty gene that causes the condition. HCM ran in the Frost family, but no one knew.

Sir David died in 2013 from a different heart problem, but the post-mortem revealed he had HCM. Miles’ brother Wilfred says: “When Miles died, we initially took a tiny bit of solace in the thought that it was a totally random thing and that nothing could have been done to prevent it. But then we discovered it was not that random, and that dad’s post-mortem showed he had the same condition, but we were never told.”

If the family had been told, they could have been tested and Miles could have been fitted with a life saving implantable cardioverter defibrillator (ICD) to restart his heart if he suffered a potentially fatal heart rhythm.

If we can stop even one of these deaths we will say Miles didn’t die in vain.

Wilfred Frost
Miles' brother

His brothers Wilfred and George have since been tested, and luckily are free from the condition. They are working with the BHF to prevent other families going through what they have endured.

Vital research

The testing Wilfred and George benefited from is possible thanks to research, much of which was pioneered by Professor Hugh Watkins, who now heads the BHF Centre of Research Excellence in Oxford. 

He has been researching HCM since 1989. In the time he’s been studying the disease, we’ve learned how to find the faulty gene that causes it, discovered there are at least nine genes involved and understood what happens in the heart of someone with HCM. “It is one of the most common serious genetic conditions,” Professor Watkins says. “When I started this research we assumed there was a gene that caused the condition. We found that there was in fact a group of genes. And in each family, the actual gene change can be one we’ve never seen before.”

Thanks to Professor Watkins’ work, people can now be tested. Genetic testing in the general population doesn’t work (as the condition isn’t common, the inevitable false results outnumber the true positives), but testing individuals with HCM and then their family members, through a process called cascade screening, works well and saves lives.

“Choosing the right treatment is a big challenge,” Professor Watkins says. Those at higher risk can have an ICD fitted. “ICDs aren’t perfect – they can deliver inappropriate shocks, so you don’t want to fit them in everybody, but they can prevent sudden death. A genetic test is an important step. If that’s positive, we do other tests so we know what their risk is. The most worrying symptom is unexplained blackouts, particularly during sport or exercise.

If someone experiences this then it’s important they see their GP and get checked out. Another danger sign is a family history of sudden deaths, and if there’s more than one of those signs we would fit an ICD.”

Future ambitions

Professor Hugh Watkins from Oxford University in a lab

Thanks to Professor Watkins and his team, new treatments are on the horizon. They established that part of the process behind HCM is the heart muscle failing to get the energy it needs. If heart cells are starved of energy, their electric system can become unstable, which leads to potentially fatal abnormal heart rhythms.

Now that we know this, an international collaboration of researchers are testing existing drugs that change how the heart gets its energy. “We are doing clinical trials looking at whether medications can change how the heart uses fuel, and whether they improve symptoms,” says Professor Watkins. “But what we want to do, and it’s looking promising, is see whether these treatments can also stop the development of the disease. “There are people who have the gene change, but their hearts look normal. What we hope is that if we give the medication early on, we can keep their hearts looking normal.”

What we hope is that if we give the medication early on, we can keep their hearts looking normal.

Professor Hugh Watkins
BHF Centre of Research Excellence, Oxford

He also wants to understand more about the genetic causes of HCM. “There are still around half of cases where a gene causing HCM is not found,” he says. “It could be that there are other genes we haven’t found yet, changes in several genes, or an interaction between genes and environmental factors, such as high blood pressure.”

Spotting patterns 

Professor Watkins says the BHF, which has funded him since 1990, has been vital to his work. “BHF support has been the backbone of my research career from the beginning,” he says. 

When he’s not working, he collects 17th-century blue-and-white Chinese and Japanese porcelain. “There is something exciting about finding rare things,” he says. “Quite a lot of doctors are collectors. We have a skill set to do with pattern recognition and having a
good eye for things.”

While pattern recognition is a bit of fun when it comes to his hobby, at work he is driven by the desire to save lives. Early in his career, Professor Watkins encountered a woman who had lost her husband and both her children to HCM. The tragedy of her situation has stayed with him. “It can be a dreadful condition,” he says. “But it’s one that can now be diagnosed and treated.” 

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