Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry.

BACKGROUND: Treatment of children with hypertrophic cardiomyopathy might be improved if the risk of death or heart transplantation could be predicted by risk factors present at the time of diagnosis. METHODS: We analysed data from the Pediatric Cardiomyopathy Registry, which collected longitudinal data for 1085 children with hypertrophic cardiomyopathy from 1990 to 2009. Our goal was to understand how patient factors measured at diagnosis predicted the subsequent risk of the primary outcome of death or heart transplantation. The Kaplan-Meier method was used to calculate time-to-event rates from time of diagnosis to the earlier of heart transplantation or death for children in each subgroup. Cox proportional-hazards regression was used to identify univariable and multivariable predictors of death or heart transplantation within each causal subgroup. FINDINGS: The poorest outcomes were recorded for the 69 children with pure hypertrophic cardiomyopathy with inborn errors of metabolism, for whom the estimated rate of death or heart transplantation was 57% (95% CI 44-69) at 2 years. Children with mixed functional phenotypes also did poorly, with rates of death or heart transplantation of 45% (95% CI 32-58) at 2 years for the 69 children with mixed hypertrophic and dilated cardiomyopathy and 38% (95% CI 25-51) at 2 years for the 58 children with mixed hypertrophic and restrictive cardiomyopathy. For children diagnosed with hypertrophic cardiomyopathy at younger than 1 year, the rate of death or transplantation was 21% (95% CI 16-27) at 2 years. For children diagnosed with hypertrophic cardiomyopathy and a malformation syndrome, the rate of death or transplantation was 23% (95% CI 12-34) at 2 years. Excellent outcomes were reported for the 407 children who were diagnosed with idiopathic hypertrophic cardiomyopathy at age 1 year or older, with a rate of death or heart transplantation of 3% (95% CI 1-5) at 2 years. The risk factors for poor outcomes varied according to hypertrophic cardiomyopathy subgroup, but they generally included young age, low weight, presence of congestive heart failure, lower left ventricular fractional shortening, or higher left ventricular end-diastolic posterior wall thickness or end-diastolic ventricular septal thickness at the time of cardiomyopathy diagnosis. For all hypertrophic cardiomyopathy subgroups, the risk of death or heart transplantation was significantly increased when two or more risk factors were present and also as the number of risk factors increased. INTERPRETATION: In children with hypertrophic cardiomyopathy, the risk of death or heart transplantation was greatest for those who presented as infants or with inborn errors of metabolism or with mixed hypertrophic and dilated or restrictive cardiomyopathy. Risk stratification by subgroup of cardiomyopathy, by characteristics such as low weight, congestive heart failure, or abnormal echocardiographic findings, and by the presence of multiple risk factors allows for more informed clinical decision making and prognosis at the time of diagnosis. FUNDING: US National Institutes of Health and Children's Cardiomyopathy Foundation.

Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: a study from the Pediatric Cardiomyopathy Registry.

BACKGROUND: Studies of cardiomyopathy in children with Noonan syndrome (NS) have been primarily small case series or cross-sectional studies with small or no comparison groups. METHODS: We used the Pediatric Cardiomyopathy Registry database to compare the survival experience of children with NS and hypertrophic cardiomyopathy (HCM) with children with idiopathic or familial HCM and to identify clinical and echocardiographic predictors of clinical outcomes. RESULTS: Longitudinal data in 74 children with NS and HCM and 792 children with idiopathic or familial isolated HCM were compared. Children with NS were diagnosed with HCM before 6 months old more often (51%) than children with HCM (28%) and were more likely to present with congestive heart failure (CHF) (24% vs 9%). The NS cohort had lower crude survival than the group with other HCM (P = .03), but survival did not differ after adjustment for CHF and age at diagnosis. Within the NS cohort (1-year survival 78%), a diagnosis of HCM before age 6 months with CHF resulted in 31% 1-year survival. Lower height-for-age z score (hazard ratio 0.26, P = .005) in place of CHF and lower left ventricular fractional shortening z score (hazard ratio 0.79, P = .04) also independently predicted mortality. CONCLUSIONS: Patients with NS with HCM have a worse risk profile at presentation compared with other children with HCM, resulting in significant early mortality (22% at 1 year). Decreased height-for-age and lower, although still supranormal, left ventricular fractional shortening z score are independent predictors of mortality in patients with NS with HCM. Such patients should have an aggressive therapeutic approach including potential listing for cardiac transplantation.

The incidence of pediatric cardiomyopathy in two regions of the United States.

BACKGROUND: Population-based data on the incidence of pediatric cardiomyopathy are rare because of the lack of large, prospective studies. METHODS: Since 1996 the Pediatric Cardiomyopathy Registry sponsored by the National Heart, Lung, and Blood Institute has collected data on all children with newly diagnosed cardiomyopathy in New England and the Central Southwest region (Texas, Oklahoma, and Arkansas) of the United States. We report on all children in these regions who received this diagnosis between 1996 and 1999. RESULTS: We identified 467 cases of cardiomyopathy, for an overall annual incidence of 1.13 per 100,000 children (95 percent confidence interval, 1.03 to 1.23). The incidence was significantly higher among infants younger than 1 year old than among children and adolescents who were 1 to 18 years old (8.34 vs. 0.70 per 100,000, P<0.001). The annual incidence of cardiomyopathy was lower among white children (upper-bound estimate, 1.06 cases per 100,000) than among black children (lower-bound estimate, 1.47 per 100,000; P=0.02) and higher among boys than among girls (1.32 vs. 0.92 per 100,000, P<0.001). The incidence also varied significantly by region: 1.44 cases per 100,000 in New England and 0.98 per 100,000 in the Central Southwest region (P<0.001). When categorized according to type, dilated cardiomyopathy made up 51 percent of the cases, hypertrophic cardiomyopathy 42 percent, and restrictive or other types 3 percent; 4 percent were unspecified. There was no significant difference in the incidence rates according to the year. CONCLUSIONS: The estimated incidence of pediatric cardiomyopathy in two large regions of the United States 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.

Ventricular remodeling and survival are more favorable for myocarditis than for idiopathic dilated cardiomyopathy in childhood: an outcomes study from the Pediatric Cardiomyopathy Registry.

BACKGROUND: Myocarditis is a cause of a new-onset dilated cardiomyopathy phenotype in children, with small studies reporting high rates of recovery of left ventricular (LV) function. METHODS AND RESULTS: The presenting characteristics and outcomes of children with myocarditis diagnosed clinically and with biopsy confirmation (n=119) or with probable myocarditis diagnosed clinically or by biopsy alone (n=253) were compared with children with idiopathic dilated cardiomyopathy (n=1123). Characteristics at presentation were assessed as possible predictors of outcomes. The distributions of time to death, transplantation, and echocardiographic normalization in the biopsy-confirmed myocarditis and probable myocarditis groups did not differ (P≥0.5), but both groups differed significantly from the idiopathic dilated cardiomyopathy group (all P≤0.003). In children with myocarditis, lower LV fractional shortening z-score at presentation predicted greater mortality (hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98; P=0.03) and greater LV posterior wall thickness predicted transplantation (hazard ratio, 1.17; 95% confidence interval, 1.02 to 1.35; P=0.03). In those with decreased LV fractional shortening at presentation, independent predictors of echocardiographic normalization were presentation with an LV end-diastolic dimension z-score >2 (hazard ratio, 0.36; 95% confidence interval, 0.22 to 0.58; P<0.001) and greater septal wall thickness (hazard ratio, 1.16; 95% confidence interval, 1.01 to 1.34; P=0.04). CONCLUSIONS: Children with biopsy-confirmed or probable myocarditis had similar proportions of death, transplantation, and echocardiographic normalization 3 years after presentation and better outcomes than those of children with idiopathic dilated cardiomyopathy. In children with myocarditis who had impaired LV ejection at presentation, rates of echocardiographic normalization were greater in those without LV dilation and in those with greater septal wall thickness at presentation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005391.

Factors associated with establishing a causal diagnosis for children with cardiomyopathy.

OBJECTIVE: The goal was to identify the clinical variables associated with establishing a cause of cardiomyopathy in children. METHODS: The Pediatric Cardiomyopathy Registry contains clinical and causal testing information for 916 children who were diagnosed as having cardiomyopathy in North America between 1990 and 1995. Children with a causal diagnosis were compared with those without with respect to several demographic, clinical, and causal testing variables. RESULTS: Cardiomyopathy was 1 of 4 types, hypertrophic (34.2%), dilated (53.8%), restrictive (3.2%), or other or mixed (8.9%). Only one third of cases had a known cause. Children with a known cause for hypertrophic cardiomyopathy were more likely to be female, to be relatively smaller, to present with congestive heart failure, and to have increased left ventricular posterior wall thickness without outflow tract obstruction. For dilated cardiomyopathy, a known cause was associated with older age, lower heart rate, smaller left ventricular dimensions, and greater shortening fraction. Family history of cardiomyopathy predicted a significantly higher rate of causal diagnoses for all cardiomyopathy types, whereas family histories of genetic syndromes and sudden death were also predictive of a cause for hypertrophic and dilated cardiomyopathies. For hypertrophic cardiomyopathy, only blood and urine testing was associated with a causal diagnosis, whereas both viral serologic testing or culture and endomyocardial biopsy were independent predictors of a causal diagnosis in dilated cardiomyopathy. CONCLUSIONS: Certain patient characteristics, family history, echocardiographic findings, laboratory testing, and biopsy were associated significantly with establishing a cause of pediatric cardiomyopathy. Early endomyocardial biopsy should be considered strongly for children with dilated cardiomyopathy, for definitive diagnosis of viral myocarditis. Although not widely used, skeletal muscle biopsy may yield a cause for some patients with hypertrophic cardiomyopathy and for patients suspected of having a mitochondrial disorder.