Genetics may explain rare heart inflammation in some young people

Gene abnormalities may make some people more susceptible to myocarditis, a rare type of heart inflammation that can affect young people and athletes.

The findings from a study led by the National Heart and Lung Institute (NHLI) and, published in Circulation, could partially answer why otherwise healthy young people sometimes develop myocarditis – a condition that can lead to heart failure and sudden cardiac death.

Myocarditis, an inflammation of the heart, is frequently 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.

In the rare instances when it happens, myocarditis "often affects young patients in the prime of life, and we've never understood why," said senior study author Professor Sanjay Prasad, a Professor of Cardiomyopathy at the NHLI and also a consultant cardiologist at Royal Brompton Hospital.

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."

Genetic factors at play

“We wanted to answer two questions: 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," said study author, James Ware, a Professor of Cardiovascular and Genomic Medicine at the NHLI and an MRC Investigator at the MRC London Institute of Medical Sciences.

The research involved two types of heart muscle disease associated with myocarditis. Dilated cardiomyopathy, the most common type, typically affects adults under age 50. It occurs when the heart muscle dilates, becoming thin and enlarging the heart's chambers, making blood pumping more difficult. In arrhythmogenic cardiomyopathy, heart muscle is replaced by scarring and fat, causing changes in heart rhythms.

Researchers analysed DNA sequencing data for 336 people with acute myocarditis and 1,053 healthy people in the UK and the Netherlands, looking for genetic variants associated with the two types of cardiomyopathy. Both groups were predominantly men.

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 those without myocarditis.

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

Importance of genetic testing 

If supported by other studies, the findings could impact care for people with myocarditis and their families, the authors said.

"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, the study's lead author and a consultant cardiologist at Royal Brompton Hospital.

"People with a family history of myocarditis or cardiomyopathy – 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," added Dr Lota.

Prasad said his team was 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.

“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,” added Professor James Ware.

'Genetic Architecture of Acute Myocarditis and the Overlap With Inherited Cardiomyopathy' by Amrit S. Lota et al is published in Circulation.

This story was adapted from a press release by American Heart Association.