Myocarditis often occurs after viral infections and may remain undetected for a long time. This is what makes myocarditis so dangerous. The heart muscle ensures with the blood circulation that the body and all its organs receive enough oxygen. If its function is compromised, it can lead to heart failure, arrhythmias, and even sudden cardiac death, especially during strenuous physical activity such as sports.

Myocarditis is one of the most common causes of heart failure and arrhythmias in children. A new study by the Experimental and Clinical Research Center Charité and the Max Delbrück Center for Molecular Medicine (ECRC), the Clinics for Congenital Heart Defects and Pediatric Cardiology of Charité and the Deutsches Herzzentrum der Charité (DHZC) in cooperation with the Competence Network for Congenital Heart Defects and the National Registry shows that genetic factors play an important role in the severity and outcome of myocarditis and provides clues on how to prevent it.

Tracking Down the Genetic Causes

In addition to viruses, genetic changes have long been suspected of playing a role in myocarditis. "Until now, there has been no explanation for the varying severity and course of myocarditis. It ranges from a simple viral infection to severe heart failure that makes heart transplantation inevitable. What we did know was that genetic cardiomyopathies, so-called primary cardiomyopathies, which originate directly in the heart muscle, often lead to heart failure," explains Professor Sabine Klaassen, head of the Clinical Cardiogenetics Research Group at the ECRC, who has been researching cardiomyopathies for many years.

"In about 30 percent of cases, genetic defects are responsible for dilated cardiomyopathy, a heart muscle disease associated with dilation of the heart chambers," says Klaassen. Together with her research team, Sabine Klaassen investigated whether such genetic changes are also involved in myocarditis and possibly even determine its course. First author of the study is Franziska Seidel from the pediatric cardiology team of the Charité and the DHZC. She has been researching myocarditis for several years as part of the MYKKE project.

Human Genetic Testing for Myocardial Disease

In comparative molecular genetic testing of tissue and DNA samples from a total of 42 young participants in the MYKKE registry who had been diagnosed with myocarditis by myocardial biopsy, the researchers found interesting differences between sample donors with dilated cardiomyopathy and those who did not have this heart disease. "Comparable studies in children based on a biopsy-proven diagnosis are scarce. Despite the comparatively small cohorts in the first step: the unambiguousness of the differences surprised us. The results contribute to a broader understanding of myocarditis and open up new possibilities for improved individualized medicine," concludes Franziska Seidel.

Younger Patients Most at Risk

On the one hand, dilated cardiomyopathy mainly affected younger children (median age 1.4 years). They also showed a significantly more severe course of myocarditis, including cardiac death. At the same time, these young patients had a significantly increased number of pathogenic gene variants in genes known to be involved in the disease.

The patients who had arrhythmias or angina pectoris, but did not have a dilated cardiomyopathy, were older (median age 16.1 years). When the researchers tested their samples using molecular genetics, they found significantly fewer pathogenic gene variants. They also had a much better recovery from myocardial inflammation.

Expanded Diagnostics Recommended

The study results now form the basis for a larger study of genetic testing in children with myocarditis in collaboration with the National Registry. At the same time, it is already possible to draw practical benefits from it: "This result provides us with valuable information for individual patient management," says Sabine Klaassen. For example, according to their new findings, the researchers strongly recommend to add molecular genetic testing to the diagnosis of children with myocarditis who also have dilated cardiomyopathy. This would allow for a better prognosis.