A recent study published in Circulation Heart Failure reports that a specific genetic variant may increase the risk of heart failure in children with myocarditis. The research found that 34.4% of children who developed dilated cardiomyopathy after experiencing myocarditis carried this gene variant, compared to just 6.3% among control children, a statistically significant difference.
Dilated cardiomyopathy occurs when the heart's main pumping chamber becomes enlarged and thin, potentially resulting in heart failure. Myocarditis, an inflammation of the heart muscle, is rare but has been identified as the leading cause of sudden death among people under 20 according to federal data.
Steven E. Lipshultz, MD, professor of pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo and corresponding author on the paper, said the findings suggest genetic testing could be valuable for all children presenting with myocarditis and cardiomyopathy. Children studied were part of the National Institutes of Health-funded Pediatric Cardiomyopathy Registry (PCMR), which Lipshultz leads.
"Historically and currently, we have always thought that particular infections lead to myocarditis with heart failure," says Lipshultz. "But many kids get infections and in fact, during the first year of life, infants get about 7 infections on average. Yet very few infants and children with infections are diagnosed with myocarditis and heart failure or sudden death."
Lipshultz has suspected an additional risk factor beyond infection alone for these severe outcomes. He noted previous research indicating that some families had genetic mutations impairing immune system protection against common viruses.
He explained his theory: "We previously found, with the help of data from the Centers for Disease Control, that some of these families had genetic mutations that made the immune systems of these children unable to protect them against common viruses."
Lipshultz describes a "double hit" model where one factor is a child’s inherited pathological cardiomyopathy mutation reducing cardiac reserve; a second factor is an infection triggering myocarditis.
"In the new study, we found that a statistically significantly greater proportion of children coming into children's hospitals and intensive care units for heart failure and new onset myocarditis had pathological cardiomyopathy gene mutations," says Lipshultz. "These mutations result in less cardiac reserve and a higher likelihood of heart failure than those with myocarditis without heart failure. So, it's very important to identify gene mutations in these patients when they are diagnosed."
He added that such mutations increase risks for recurrent episodes and sudden cardiac death, making affected patients candidates for implantable cardiac defibrillators.
The recommendation from Lipshultz is clear: "The bottom line for clinicians... if you don't look for pathologic genetic mutations, then you won't know if the patient is at higher risk for sudden death. But if you do look and you find concerning risk factors, you should act," he says.
This work was recognized as a “Top Pediatric Cardiology Research” award at last year's American Heart Association Scientific Sessions by first author Alicia Kamsheh, MD (Washington University School of Medicine). Stephanie Ware, MD, PhD (Indiana University School of Medicine) led genetics studies related to this research.
Researchers from several institutions collaborated on this project including Washington University School of Medicine; Indiana University School of Medicine; Cincinnati Children's Hospital; University of Cincinnati; Columbia University Medical Center; University of Tennessee Health Science Center; Le Bonheur Children's Hospital; Keck School of Medicine at USC; Children's Hospital Los Angeles; University of Utah; Primary Children's Hospital; Mount Sinai Kravis Children's Hospital; Icahn School of Medicine; Helen DeVos Children's Hospital and Boston Children's Hospital.
Danielle Dauphin Megie coordinated study efforts along with colleagues from UB Department of Pediatrics. Funding was provided by National Heart, Lung and Blood Institute PCMR and Pediatric Cardiomyopathy Genes study as well as support from organizations such as Children’s Cardiomyopathy Foundation, Kyle John Rymiszewski Foundation and Sofia’s Hope Inc.
