Researchers from the MRC London Institute of Medical Sciences (LMS) have discovered rare genetic mutations can identify people who are at a 70% increased risk of serious heart problems in the future.

Hypertrophic Cardiomyopathy (HCM) affects an estimated 1 in 500 people in the UK. It is triggered by genetic mutations that cause the heart muscle to become thicker, which make it harder for the heart to pump blood around the body. This can cause symptoms ranging from palpitations to sudden cardiac death.

HCM is the most common inherited heart condition, but cases of sudden cardiac death are sometimes seen outside of affected families. To assess the impact of HCM genetic mutations in the wider population, researchers from the Computational Cardiac Imaging and Cardiovascular Genomics and Precision Medicine groups at the MRC LMS analysed data from over 200,000 participants in UK Biobank.

The researchers found that almost 1 in 400 people carried a genetic change known to be associated with HCM which resulted in almost a 70% increased risk of experiencing an adverse cardiac event, including irregular heart rhythm, stroke, heart failure and cardiac arrest. Interestingly, the researchers noticed these genetic changes could be found in people not yet showing any symptoms of HCM.

To further investigate the impact of HCM genetic mutations on heart physiology, 40,000 of the 200,000 UK Biobank participants were invited to have a cardiac magnetic resonance imaging (CMR) scan. The scan produces detailed images of the structures within and around the heart. Artificial intelligence was used to analyse and measure the thickness of each person’s heart muscle.

The images revealed that although the heart muscle was mildly thicker in people carrying HCM-associated genetic mutations, less than 10% would be diagnosed as having possible disease. The risk of future events was also not completely dependent on developing abnormal thickening of the heart.

This observation suggests that other factors, such as fibrosis (scarring and stiffening) of the heart muscle, could be a factor in people carrying these genetic variants (Ho et al. NEJM 2010).

Dr Antonio de Marvao, MRC Chain-Florey Clinical Lecturer in Cardiology and first author of the paper said:

“The use of powerful artificial intelligence computer programmes allowed us to perform a combined analysis of MRI heart scans, genetic and health information of over 200,000 people. We found that individuals with certain rare genetic variants, known to cause hypertrophic cardiomyopathy, are at significantly increased risk of developing heart failure and dangerous heart rhythms, even if they do not have abnormally thick hearts.”

Professor Declan O’Regan, Head of the Computational Cardiac Imaging group at the MRC LMS and joint senior author commented on the clinical impact of this research:

“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.”

‘Phenotypic Expression and Outcomes in Individuals With Rare Genetic Variants of Hypertrophic Cardiomyopathy‘ was published 06 September 2021 in the Journal of the American College of Cardiology. This study is part-funded by the British Heart Foundation.