Identifying High-Risk Patients in Children With Heart Failure

Dilated cardiomyopathy is the most common type of cardiomyopathy in children. It prevents the heart from pumping blood effectively because the main pumping chamber of the heart is too stretched out.

According to data published in 2003 by the Pediatric Cardiomyopathy Registry (PCMR) in the New England Journal of Medicine, the estimated incidence of pediatric cardiomyopathy is 1.13 cases per 100,000 children. Most cases are identified at an early age, and the incidence varies according to sex, region, and racial or ethnic origin.

Funded by Amgen Inc., the research was conducted at multiple sites in the U.S. and Canada participating in the PCMR, which was founded more than 25 years ago by Steven E. Lipshultz, MD, A. Conger Goodyear Professor and Chair of pediatrics and principal investigator on the Amgen research.

The registry was developed to collect and organize relevant data on the condition, with the goal of increasing awareness of the condition and its causes, as well as to spur new diagnostic and therapeutic interventions. Lipshultz is director of the registry.

“Until recently, there was no improvement in medical management for children with dilated cardiomyopathy and heart failure and, as a result, this has been the leading cause of heart transplantation in children 2-18 years of age around the world,” says Lipshultz, who co-authored the paper and is also president of UBMD Pediatrics.

“More than half of these children have died or needed heart transplant within the first two years after presentation,” Lipshultz says. “This represents some of the worst outcomes seen by pediatric cardiologists.”

A total of 557 patients, recruited from the PCMR, were included in the study. According to the findings, of the 192 children with an elevated heart rate, 38 (19.8 percent) died without heart transplant (which may have saved them); among the 365 children with a normal heart rate, 39 (10.7 percent) died without heart transplant.

In children in the study who had an elevated heart rate, the median heart rate was 149 as compared to a median heart rate of 119 among the children with a normal heart rate.

The findings are especially significant, Lipshultz says, because most established risk factors for poor outcomes in children with dilated cardiomyopathy, such as patient age, cause of cardiomyopathy and the size and function of the left ventricle, ­cannot be modified by clinical intervention.

“Heart rate hasn’t previously been seen as a risk factor for poor outcomes in children with dilated cardiomyopathy,” Lipshultz explains. “This research suggests that heart rate may, in fact, serve as an important ‘biomarker’ in this population, and that reducing heart rate could turn out to be a key therapeutic target for these children.”

These observational findings provide the impetus for more study to assess the utility of therapies that control elevated heart rate and how they might improve the survival of these children, he adds.

“This research shows that the child’s resting heart rate is one of the strongest predictors of future survival or avoiding a heart transplant in these patients with dilated cardiomyopathy and heart failure who present to cardiologists in the PCMR,” Lipshultz says.  

He notes that for children with higher resting heart rates, even when controlling for other factors that could confound this result, a higher resting heart rate portents a significantly worse clinical outcome, with much higher rates of failing medical management and needing a heart transplant or dying.

“These new findings are important for the identification of high-risk patients who might benefit from early listing for a heart transplant since donor availability is often limited, and also for family counseling and planning,” Lipshultz explains.

He adds that some of the newest potentially effective therapies for treating heart failure in children target heart rate and their effect is to lower heart rate in these patients. 

“New studies are already underway, investigating this testable hypothesis for children with heart failure and dilated cardiomyopathy to see if lowering heart rate with these new classes of therapy that have never been used in these children before improve their outcomes,” Lipshultz says.

The Pediatric Cardiomyopathy Registry is funded by the National Heart, Lung and Blood Institute and the Children’s Cardiomyopathy Foundation.

The paper’s first author is Joseph W. Rossano, MD, co-director of the Cardiac Center and chief of the Division of Cardiology at Children’s Hospital of Philadelphia.

Other co-authors of the study are from the following companies and institutions:

• Amgen Inc.
• Children’s Hospital Los Angeles
• New England Research Institutes
• University of Tennessee
• Vanderbilt University
• Wayne State University