Spanish scientists have discovered a biomarker, a type of microRNA, that can be used to distinguish patients with myocarditis from those who have had a myocardial infection, something that could help improve treatment for this condition.
Myocarditis, also known as inflammatory cardiomyopathy, is caused by inflammation of the heart muscle, most often due to a viral infection, although it can be caused by other things. It impacts around 1-2 million people around the world each year, often those who are young and otherwise healthy, and ranges from mild to severe in symptoms.
It can be difficult to diagnose myocarditis as it has similar clinical features to several other cardiovascular health problems including the after effects of a heart attack or myocardial infarction, as well as some autoimmune inflammatory conditions. As these can require different treatment types and follow up it is important to differentiate between the two as soon as possible.
Researchers from the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, led by Pilar Martín, Ph.D., carried out a study to try and identify a biomarker specific to patients with myocarditis.
They first carried out a study in a mouse model of myocarditis and myocardial infarction to search for a potential biomarker. The researchers found that CD4+ type 17 helper T (Th17) cells were specifically released in animals with myocarditis as a marker of heart muscle damage caused by the inflammation. The Th17 cells synthesize a micro(mi)RNA — mmu-miR-721—that was present in the plasma of mice with myocarditis but not myocardial infarction.
“We identified miR-721 in the blood plasma of mice with autoimmune or viral myocarditis. This miRNA is produced by autoimmune Th17 cells that recognize cardiac antigens derived from proteins such as alpha-myosin,” says Rafael Blanco-Domínguez, a graduate student at CNIC and first author on the New England Journal of Medicine paper describing the work.
Co-first author Raquel Sánchez-Díaz, Ph.D., a postdoc at CNIC, explains that “these cells attack the myocardium, and are in large part responsible for the pathophysiology of the disease.”
Following the mouse study, the team identified an equivalent miRNA marker in humans — hsa-miR-Chr8:96. In four independent cohorts of almost 500 people including controls, patients with myocardial infarction and those with myocarditis, the researchers confirmed that this miRNA is a good differentiating marker.
In a statistical analysis, the area under the receiver-operator curve for hsa-miR-Chr8:96’s ability to distinguish patients with acute myocarditis from those with myocardial infarction was 0.927. This relationship was still valid after correcting for age, gender, ejection fraction and troponin level.
“Our finding has great potential as a valuable clinical tool for the precise and noninvasive diagnosis of myocarditis from small drops of blood,” says Martín.
The team is now validating their finding further and is also looking at whether this biomarker can also indicate short or long-term risk of developing this cardiac condition.