Treating Children with Idiopathic Dilated Cardiomyopathy (From the Pediatric Cardiomyopathy Registry)

In 40% of children with symptomatic idiopathic dilated cardiomyopathy (IDC), medical therapy fails within 2 years of diagnosis. Strong evidence-based therapies are not available for these children, and how evidence-based therapies for adults with IDC should be applied to children is unclear. Using data from the National Heart, Lung, and Blood Institute’s Pediatric Cardiomyopathy Registry, we compared practice patterns of initial therapies for children with IDC diagnosed between 1990 and 1995 (n=350) and between 2000 and 2006 (n=219). At diagnosis, 73% had symptomatic heart failure, and 7% had one or more family members with IDC. Anti-heart failure medications were most commonly prescribed initially. Anti-heart failure medication use was similar across both time periods (84% and 87%, respectively), as was angiotensin-converting enzyme inhibitor (ACEI) use (66% and 70%, respectively). These medications were used more commonly in children with greater left ventricular dilation and poorer left ventricular fractional shortening and functional class (P<0.001). Beta-blocker use ranged from 4% to 18% over the two time periods. Treatments for pediatric IDC have changed little over the past 25 years. Anti-heart failure medications remain the most common treatment, and they are often given to children with asymptomatic left ventricular dysfunction. Children with asymptomatic left ventricular dysfunction are often not offered ACEIs without echocardiographic evidence of advanced disease. Therapeutic clinical trials are strongly indicated because practice variation is substantial and medical outcomes in these children have not improved in the past several decades

Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the Pediatric Cardiomyopathy Registry

Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients <18 years of age with HCM, 8.7% (n=74) had inborn errors of metabolism, 9.0% (n=77) had malformation syndromes, 7.5% (n=64) had neuromuscular disorders, and 74.2% (n=634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (n=227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (n=407). Patients with idiopathic HCM who survived to at least 1 year of age, however, had an annual mortality rate of 1% that was similar regardless of whether they were diagnosed before or after 1 year of age. In children, HCM is a diverse disorder with outcomes that depend largely on cause and age. Patients presenting before 1 year of age have the broadest spectrum of causes and the poorest outcome. In those children with idiopathic HCM who survive beyond age 1, however, survival is independent of age at diagnosis, with an annual mortality rate (1%) that is much lower than previously reported in children and is not different from has been found in population-based studies in adults

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

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. 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. 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. 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

Factors Associated With Establishing a Causal Diagnosis for Children With Cardiomyopathy

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Abstract 2556: A Comparative Analysis of Outcomes for Pediatric Patients with Biopsy-Proven Myocarditis, Clinically-Diagnosed Myocarditis and Idiopathic Dilated Cardiomyopathy

Background: Data on outcomes in children with myocarditis is sparse and challenging to interpret given no ``gold standard” for diagnosis. The NHLBI Pediatric Cardiomyopathy Registry provides a large, multi-center cohort with clinical and echocardiographic follow-up of up to 16 years. Methods/Results : We compared cases of biopsy-confirmed myocarditis (BCM, N=119) and clinically-diagnosed myocarditis (CDM, N=253), with idiopathic dilated cardiomyopathy (IDCM, N=1123). BCM and CDM patients were older at diagnosis than those with IDCM (median age 1.6, 1.9, 1.2 yr, respectively). For BCM, heart failure symptoms (86%) and admission (97%) at diagnosis were more common (p2) in 71% with myocarditis and 86% with IDCM. Systolic function was impaired in all groups, with a median fractional shortening (FS) Z score of -9 for myocarditis and -10 for IDCM; 23% of myocarditis patients had impaired function without dilation. Two-year death/transplant rates were 24% (BCM), 24% (CDM), and 47% (IDCM). Of myocarditis survivors, 46% had normalization of both EDD and FS Z-scores at 2 years vs. 25% for IDCM (p<.0001). Baseline echo status was strongly associated with later echo status for IDCM pts. Recovery from myocarditis at 2 years was not strongly associated with baseline echocardiographic characteristics, but transplant-free survival was lower in myocarditis patients when both baseline FS and EDD were abnormal (logrank p=.03). When therapeutic data were available, the BCM group received IVIG/steroids most often (44% vs. 23% CDM, 6% IDCM); this was not significantly associated with 2-year echo recovery or transplant-free survival, but power was limited. Conclusions : In this dataset, children with BCM and CDM have similar profiles and a better outcome than those with IDCM, with 76% surviving without transplant at 2 years. Nearly 1 / 2 have normalization of LV size and function, but the presence of both dilation and poor function at presentation is associated with increased risk for death or transplant. Echocardiographic normalization occurs in 25% of IDCM survivors by 2 years. This study is limited by being an analysis of available information in a database collected for other purposes

Health-Related Quality of Life and Functional Status Are Associated with Cardiac Status and Clinical Outcome in Children with Cardiomyopathy

To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes. Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥ 5 years) and Functional Status II (Revised) (age ≤ 18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL. The 355 children evaluated at ≥ 5 years (median 8.6 years) had lower functioning (CHQ Physical and Psychosocial Summary Scores 41.7 ± 14.4 and 47.8 ± 10.7) than that of healthy historical controls. The most extreme CHQ domain score, Parental Impact-Emotional, was one SD below normal. Younger age at diagnosis and smaller left ventricular end-diastolic dimension z score were associated independently with better physical functioning in children with dilated cardiomyopathy. Greater income/education correlated with better psychosocial functioning in children with hypertrophic and mixed/other types of cardiomyopathy. In the age ≥ 5 year cohort, lower scores on both instruments predicted earlier death/transplant and listing for transplant in children with dilated and mixed/other types of cardiomyopathy (P < .001). Across all ages (n = 565), the Functional Status II (Revised) total score was 87.1 ± 16.4, and a lower score was associated with earlier death/transplant for all cardiomyopathies. HRQOL and functional status in children with cardiomyopathy is on average impaired relative to healthy children. These impairments are associated with older age at diagnosis, lower socioeconomic status, left ventricular size, and increased risk for death and transplant. Identification of families at risk for functional impairment allows for provision of specialized services early in the course of disease. ClinicalTrials.gov: NCT00005391

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

Population-based data on the incidence of pediatric cardiomyopathy are rare because of the lack of large, prospective studies. 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. 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. 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