New research has unearthed genetic differences that increase a person’s risk of heart problems and sudden cardiac arrest.

The study, the largest of its kind, found that rare genetic differences were present in individuals who had no visible changes to their heart. The discovery of these genetic differences behind the increase in a person’s risk of heart problems may provide an opportunity to identify people before they even have symptoms. The research, co-led by Professor Declan O’Regan (MRC London Institute of Medical Sciences) and Dr James Ware (National Heart and Lung Institute), Imperial, was funded by the British Heart Foundation (BHF).

"This research may help to spot those at greater risk of sudden heart death even before any typical signs of disease are seen" Professor Declan O'Regan Co-lead author

Normally these rare genetic differences are found in people with hypertrophic cardiomyopathy (HCM). HCM is passed down through families and causes the heart wall to become thickened. This thickening causes an increased chance of stroke, abnormal heart rhythm, heart failure, and cardiac arrest.

Through this research scientists have found that most people with these rare genetic changes don’t develop HCM. However, the changes can increase a person’s risk of heart problems even when they don’t have the typical features of cardiomyopathy. These findings may pave the way for new tools to identify those at risk of sudden cardiac death, irregular heart rhythm, stroke and heart failure.

Professor Declan O’Regan comments “With the rise of clinical as well as commercial genetic screening, more people than ever are able to have their genome sequenced. This research may help to spot those at greater risk of sudden heart death even before any typical signs of disease are seen. In future combining genetic testing with advanced heart imaging could help to prevent unexpected deaths particularly in young adults.”

The researchers looked for rare mutations in approximately 200,000 adults using the UK Biobank database. They then determined if these genetic changes influenced the likelihood of developing cardiomyopathy or suffering irregular heart rhythm, stroke, heart failure and cardiac arrest. Scientists found the genetic changes were linked to an increased risk of serious heart problems and cardiac death. These changes were present in 1 in 407 people.

Video shows how AI is used to track the shape and motion of the heart on cardiac MRIs in UK biobank participants

Over 40,000 of the 200,000 people were invited to have a cardiac magnetic resonance imaging (CMR) scan. Images were taken of their hearts and the thickness of the heart muscle walls were measured using artificial intelligence analysis. Surprisingly, in the people with these genetic changes, there was sometimes an increased risk of cardiac death even when there was little or no thickening in the heart shown in the images.

“With increasing availability of DNA sequencing, more and more people are found to carry a faulty copy of a cardiomyopathy gene even when they are not aware of any problem with their heart, and nobody has been sure how important these genetic changes are. This study tells us that most people will not develop full-blown cardiomyopathy, which is reassuring. However, a minority do run into problems – and we are developing tools that will tell us who we need to keep a close eye on to prevent problems in the future" explains Dr James Ware.

This research is an important step towards understanding the reason why some people suffer sudden cardiac death while others do not. It could lead to population wide genetic testing that could spot individuals at risk of sudden cardiac death who have no visible abnormalities in their hearts.

Read the full publication in the Journals of the American College of Cardiology – 'Phenotypic Expression and Outcomes in Individuals With Rare Genetic Variants of Hypertrophic Cardiomyopathy'. 

The co-leads would like to note the substantial contributions by Antonio de Marvao, Kathryn McGurk and Sean Zheng to this research.