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HOUSTON -- Pediatric dilated cardiomyopathy is a diverse disorder with outcomes that depend largely on cause, age, and heart failure status at presentation, as well as sex and race, according to researchers here.
HOUSTON, Oct. 19 -- Dilated cardiomyopathy in children is a diverse disorder with outcomes that depend largely on cause, age, and heart failure status at presentation, as well as sex and race, according to researchers here.
Only 34% of pediatric patients have an identifiable cause, while the spectrum of disease etiologies in children is quite different from that reported for adults, Jeffrey Towbin, M.D., of Baylor College of Medicine here, and colleagues, reported in the Oct. 18 issue of the Journal of the American Medical Association.
These findings come from a longitudinal study of 1,426 children younger than 18 years in North America.
The study combined two similar cohorts-- a population-based, prospective group of children diagnosed since Jan. 1, 1996, at 89 pediatric cardiac centers and a retrospectively collected group seen primarily at large tertiary-care centers, diagnosed from 1990 to 1995, and enrolled through February 2003.
The annual incidence of dilated cardiomyopathy in children younger than 18 years was 0.57 cases per 100,000 per year overall, a rate 10% of that in adults, Dr. Towbin said. This may relate to fewer chronic health-habit risk factors, a longer latency period for clinical expression of the effects of genetic and environmental factors on the heart, and the wider age span of adulthood compared with childhood, he said.
Other findings were: The median age at time of diagnosis was 1.5 years. The median age at transplantation was 4.8 years. For all patients who died, death occurred at a median of three years.
The annual incidence was higher in boys than in girls (0.66 vs. 0.47 cases per 100 000; P<. 001).
Rates were also higher in blacks than in whites (0.98 vs. 0.46 cases per 100 000; P< .001), and causes were different.
Infants had more than 13 times the incidence of older children (4.40 vs. 0.34 cases per 100 000; P<. 001).
The majority of children (66%) had idiopathic disease, which limited the potential for disease-specific therapies.
In those with known etiology, myocarditis (46%) and neuromuscular disorders (26%) were the most common causes, with familial disease, inborn errors of metabolism, and malformation syndromes less common. In adults, coronary artery disease, which is rare in childhood, is a common cause of the cardiomyopathy and explains some of the differences between the rates in childhood versus adulthood.
Most of the children with neuromuscular disorders had Duchenne (80%) or Becker muscular dystrophy (10%). The majority of those with the familial form had autosomal dominant inheritance (68%), while 24% had autosomal recessive inheritance. Among 54 patients with inborn errors of metabolism, the largest subgroup was mitochondrial disorders (46%), followed by Barth syndrome (24%).
The one-year and five-year rates of death or transplantation were 31% and 46%, respectively. Independent risk factors at diagnosis for subsequent death or transplantation were older age, congestive heart failure, lower left ventricular fractional shortening Z score, and cause of DCM (P <. 001 for all).
Worse outcomes were associated with older age, worse ventricular dysfunction at presentation and more advanced congestive heart failure. Of the patients, 71% had congestive heart failure.
Outcomes by cause varied widely from 57% to 94% survival at five years, Dr. Towbin said, This suggests the need to establish an etiology to determine the subsequent optimal management and to more accurately predict prognosis. However, he said, understanding the cause remains difficult, with only 34% of pediatric patients having an identifiable cause.
Mortality and cardiac transplantation did not match for specific causes. There was a lower mortality but a higher rate of cardiac transplantation for familial dilated cardiomyopathy compared with idiopathic. This, the investigators said, raises questions about optimal transplantation management.
One conclusion would be that patients with idiopathic disease are not undergoing transplantation as often as they should or that more needs to be done to establish etiologies for idiopathic dilated cardiomyopathy in children.
Similar questions, the investigators said, are raised for myocarditis, in which deaths continue to occur years after presentation. The continuing mortality risk contradicts the previously held belief of a high recovery rate in this population.
In discussing the study's limitations, the researchers said their study probably underestimated the heart disease incidence because subclinical cases were, by definition, not completely captured by the study's methods. In addition, the large percentage of infants and children with no known etiology reduced the predictability of etiology-based outcomes.
The regions participating in the study may not have been fully representative of the U.S., and finally, they said, the observational nature of the study plus the fact that detailed treatment data were not collected from all participants precluded reliable conclusions about the relationship between therapy and outcomes. However, they said, therapies have not been shown to affect outcomes dramatically.
"Despite the billions of dollars used to care for these patients, develop new therapies, and perform genetics-based studies, survival is still poor," Dr. Towbin and his colleagues wrote.
"New methods for early diagnosis and risk stratification, as well as new therapies, need to be developed for infants and children with dilated cardiomyopathy to avoid transplantation and premature death. The identification of patient characteristics and underlying diseases with the worst and best outcomes should enable focused investigations regarding these issues," they concluded.