Research Urged on Heart Muscle Disease in Children

Steven E. Lipshultz, MD

Published July 23, 2019

Cardiomyopathy is a heart condition involving abnormalities of the muscle fibers, which contract with each heartbeat. Nearly half of children with this type of heart disease either undergo a heart transplant or die within two years of being diagnosed.

“These findings are concerning because they often result in unimaginable suffering for these children and their families. For this reason, research in pediatric cardiomyopathy is urgently needed.”
Steven E. Lipshultz, MD
A. Conger Goodyear Professor and Chair of the Department of Pediatrics

That somber statistic is part of an American Heart Association (AHA) scientific statement published in the July issue of the journal Circulation.

A writing group led by Steven E. Lipshultz, MD, A. Conger Goodyear Professor and Chair of the Department of Pediatrics, produced the statement.

Published Researched on Disease is Sparse

The AHA asked Lipshultz to chair the group in 2016 to assess the current state of the field of cardiomyopathy in children, in terms of classification and diagnosis.

Pediatric cardiomyopathy occurs in approximately 1 in 100,000 U.S. children. In many cases, it means that the heart isn’t pumping blood efficiently.

Symptoms can include shortness of breath, arrhythmias, dizziness, swollen hands and feet, as well as other indications.

The authors point out that while children are afflicted with the condition at roughly the same incidence as some childhood cancers — including lymphoma, Wilms tumor and neuroblastoma — the quantity of “published research and scientific conferences focused on pediatric cardiomyopathy are sparser than for those cancers.”

Statement Proposes New Classification Scheme

The AHA statement proposes a new classification scheme for cardiomyopathy in children.

“Our new classification systems are controversial,” Lipshultz says. “We follow a hierarchical classification of cardiomyopathy in children that places morphofunctional characteristics higher than genetic and nongenetic causes of disease.”

“This places children with syndromes known to be associated with their heart disease, such as Noonan syndrome patients with a hypertrophied left ventricle, within rather than outside of this classification scheme, as their structural heart disease meets the phenotypic definition of hypertrophic cardiomyopathy,” he adds.

“This also places children with a genotypic predisposition, such as pathogenic MYH7 mutation, outside rather than within this classification scheme if they show no cardiomyopathy phenotype.”

Aiming to Determine Future Research Priorities

The purpose of the scientific statement is to help determine future research priorities in order to “achieve earlier diagnosis, improved clinical outcomes and better quality of life for these children and their families.”

While heart muscle disease in children is rare, the authors note that it can result in “some of the worst pediatric cardiology outcomes.”

For example, until recently, the percentage of children with cardiomyopathy who underwent a heart transplant had not declined, and the condition remains the leading cause of transplantation for children older than 1 year.

“These findings are concerning because they often result in unimaginable suffering for these children and their families,” Lipshultz says. “For this reason, research in pediatric cardiomyopathy is urgently needed.”

New Therapies Under Development

For example, he mentions a multicenter study that he led involving 98 centers across the U.S. and Canada and conducted by the National Institutes of Health-supported Pediatric Cardiomyopathy Registry.

“This study showed that for children with heart failure from dilated cardiomyopathy — where the heart’s main pumping chamber is enlarged and weakened — there has been a dramatic improvement in outcomes of medical management in the past few years and significantly fewer of these patients die from heart disease,” Lipshultz says.

Results from this international study also showed, for the first time, improved transplant-free survival rates for pediatric dilated cardiomyopathy patients.

But Lipshultz notes there is still much more work to do.

Although heart transplantation has improved outcomes for children with dilated cardiomyopathy, it is limited by donor heart availability. Lipshultz says that new therapies — including new medications, advanced intensive care and artificial heart machines, and comprehensive chronic illness management — are now being used to treat children with dilated cardiomyopathy.

Lipshultz Helped Create Registry, Foundation

The authors note that according to studies from the Pediatric Cardiomyopathy Registry, the cause of the disease remains unknown in the vast majority of cases, another reason why more research is needed.

While classification and causes of cardiomyopathies in infancy, childhood and adolescence can have similarities with those seen in adults, the statement cautions that many pediatric cases have unique pathogeneses and risk factors, and the disease progresses differently from cases in adults.

Because of the lack of data on pediatric cardiomyopathies, the group concluded that it couldn’t provide evidence-based guidelines. “Rather, we have given a current perspective of the state of this field to illustrate what is known and where knowledge gaps exist for future discovery.”

Many of the findings reported in the AHA scientific statement were conducted through the Pediatric Cardiomyopathy Registry, founded by Lipshultz and his colleagues in 1990 to study the outcomes of children with various heart muscle disorders.

The registry is sponsored by the NIH and the Children’s Cardiomyopathy Foundation, which was founded in 2001 with Lipshultz’s help by Lisa Yue, now its president and the mother of two sons who died from cardiomyopathy. Lipshultz chairs its medical advisory board, which partners with the AHA on funding research grants.

Sharing Best Practices to Improve Outcomes

Lipshultz says recent findings from the registry demonstrate the value of leading pediatric heart centers throughout North America gathering information and sharing best practices to improve outcomes.

“We have been able to reduce failure of medical management by about 50 percent, which translates to a large number of children with dilated cardiomyopathy who are alive without heart transplant, compared to children with dilated cardiomyopathy at the same centers in the past who would not have survived or would have needed a heart transplant,” he says.

“When you consider that in this population, fully half the children who are living today would not have survived in the past, this is truly incredible.”

That research was published in the Journal of the American College of Cardiology in 2017.

Many Current Studies Coordinated in Buffalo

Lipshultz is the principal investigator of a number of NIH grants that are actively studying pediatric cardiomyopathy to promote discovery and reach better outcomes, with many of these studies now being coordinated in Buffalo.

Lipshultz is also pediatric chief-of-service at Kaleida Health, medical director of pediatric services business development at Oishei Children’s Hospital and president of UBMD Pediatrics.

One is evaluating the heart status of children who have been exposed to, and treated for, viral infections, with the goal of understanding the causes of the cardiomyopathies that they later developed. Another is a 30-year longitudinal study focused on the long-term outcomes of patients who took a medication designed to provide short-term protection against heart damage.

Writing group co-authors are:

  • Alfred Asante-Korang, MD, Johns Hopkins All Children’s Heart Institute
  • Eric D. Austin, MD, Vanderbilt University Medical Center
  • Steven D. Colan, MD, Boston Children’s Hospital
  • Anne I. Dipchand, MD, Hospital for Sick Children, University of Toronto
  • Melanie D. Everitt, MD, University of Colorado
  • Daphne T. Hsu, MD, Albert Einstein College of Medicine and Children’s Hospital at Montefiore
  • Yuk M. Law, MD, (vice chair of group), Seattle Children’s Hospital
  • Kimberly Y. Lin, MD, Children’s Hospital of Philadelphia and University of Pennsylvania
  • Jack F. Price, MD, Texas Children’s Hospital
  • James D. Wilkinson, MD, Vanderbilt University Medical Center