Genetics may explain rare heart inflammation in young people and athletes

 30 September 2022  

New research from the Cardiovascular Genomics and Precision Medicine group at the MRC Laboratory of Medical Sciences has shown that one in 13 people who get myocarditis, a rare type of heart inflammation, carry genetic variants that make them more vulnerable to the condition. 

Graphic of a transparent male torso with heart visibleGene abnormalities may make some people more susceptible to myocarditis, a rare type of heart inflammation that can affect young people and athletes, a large new study finds. 

The findings, published Monday in Circulation, could partially answer why otherwise healthy young people sometimes develop a condition that can lead to sudden death and heart failure, researchers said.  

“We wanted to answer two questions,” said Professor James Ware, a lead author on the study who leads the Cardiovascular Genomics and Precision Medicine group and is a consultant cardiologist at the Royal Brompton Hospital. “Why do some people develop myocarditis, while others don’t, and then why do some people with myocarditis have reduced pump function (heart failure)? We found that different genetic factors were at play in each case.” 

“Myocarditis often affects young patients in the prime of life, and we’ve never understood why,” said senior study author Dr. Sanjay Prasad, a professor of cardiomyopathy at Imperial College London. 

The new, population-based study suggests that “it’s not just random,” he said. “For a subset of people, there’s a gene that predisposes them to this, or makes them susceptible.” 

“This study highlights the importance of a collaborative approach, involving scientists from different disciplines at the LMS, NHLI, local NHS and academic partners (including the NIHR Imperial BRC and BHC Centre of Research Excellence), and international colleagues.” said James. 

Myocarditis, a rare inflammation of the middle layer of the heart muscle wall, is often triggered by a virus. The condition can progress to heart muscle disease that weakens the heart and its ability to pump blood. Myocarditis usually resolves on its own or with treatment, but in some cases it can cause lasting damage and even be fatal. 

Previously undetected and untreated myocarditis has been identified as the cause of sudden death in 8% of 1 to 17-year-olds and 9% of athletes. Postmortem studies suggest it may be responsible for 3% to 12% of all sudden cardiac deaths. 

In this study, the researchers analysed DNA sequencing data for 336 patients with acute myocarditis and 1,053 healthy people in London and the Netherlands, looking for genetic variants associated with two types of cardiomyopathy. 

The participants were followed for five years. Among those who had myocarditis, 8% – or 1 in 13 – had genetic variants associated with the cardiomyopathies, compared with fewer than 1% of the healthy study participants. 

While this data was collected between 2016 and 2018, prior to the COVID-19 pandemic, the team are now studying whether a subset of people with COVID-19-related myocarditis also had these genetic variants. 

If supported by other, similar studies, the findings could impact care for patients with myocarditis and their families. 

“These findings suggest there should be a low threshold for genetic testing in patients who present with myocarditis – particularly when there isn’t an obvious reason for it,” said Dr. Amrit Lota, also a consultant cardiologist at Royal Brompton Hospital in London and lead author on the study. 

People with a family history of myocarditis – along with young patients with poor heart function, frequent heart rhythm disturbances or who have a lot of scarring on heart MRIs – also should be considered for testing, he said. 

The team are continuing to follow the people in this study – as well as expanding it to include more patients – to find out how those with the genetic variants fared over the long-term. Future investigations also would analyse data across ethnicities and gender to look for differences among specific groups.