The Pediatric Cardiomyopathy Registry: 1995–2007

doi:10.1016/j.ppedcard.2007.11.006

Progress in Pediatric Cardiology

Volume 25, Issue 1, April 2008, Pages 31-36

https://doi.org/10.1016/j.ppedcard.2007.11.006 Get rights and content

Abstract

Cardiomyopathy is a serious disorder of the heart muscle and, although rare, it is potentially devastating in children. Funded by the National Heart Lung and Blood Institute since 1994, the Pediatric Cardiomyopathy Registry (PCMR) was designed to describe the epidemiology and clinical course of selected CMs in patients 18 years old or younger and to promote the development of etiology-specific prevention and treatment strategies. Currently, data from more than 3000 children with cardiomyopathy have been entered in the PCMR database with annual follow-up continuing until death, heart transplant, or loss-to-follow up. Using PCMR data, the incidence of cardiomyopathy in two large regions of the United States is estimated to be 1.13 cases per 100,000 children. Only 1/3 of children had a known etiology at the time of cardiomyopathy diagnosis. Diagnosis was associated with certain patient characteristics, family history, echocardiographic findings, laboratory testing, and biopsy. Greater incidence was found in boys and infants (< 1 yr) for both dilated and hypertrophic cardiomyopathy (DCM, HCM) and black race for only DCM. In DCM, prognosis is worse in older children (> 1 yr), heart failure (HF) at diagnosis or idiopathic etiology. For HCM, worse prognosis is associated with inborn errors of metabolism or combination of HCM and another cardiomyopathy functional type. The best outcomes were observed in children presenting at age > 1 yr with idiopathic HCM. PCMR data have enabled analysis of patients with cardiomyopathy and muscular dystrophy, as well as Noonan Syndrome. Currently, collaborations with the Pediatric Heart Transplant Study group and a newly established Pediatric Cardiomyopathy Biologic Specimen Repository at Texas Children's Hospital will continue to yield important results. The PCMR is the largest and most complete multi-center prospective data resource regarding the etiology, clinical course and outcomes for children with cardiomyopathy.

Introduction

In 1994, the National Heart, Lung and Blood Institute (NHLBI) provided funding for the establishment of the Pediatric Cardiomyopathy Registry (PCMR), a large, multi-center observational study of primary and idiopathic cardiomyopathies in children. The PCMR was designed to describe the epidemiology and clinical course of selected cardiomyopathies in patients 18 years old and younger, and to promote the development of etiology-specific prevention and treatment strategies. Currently, data from more than 3000 children with cardiomyopathy have been entered in the PCMR database with annual follow-up continuing until death, heart transplant, or loss-to-follow up. The aims of the PCMR have evolved over the 14 years of continuous NHLBI funding. The original aims were primarily epidemiological with the establishment of retrospective and prospective cohorts to estimate the incidence and outcome in children with cardiomyopathies overall, as well as within subgroups defined by gender, age, race, and geographic residence. In the second grant cycle, parent-reported functional status data were prospectively collected to better characterize the impact of cardiomyopathy on the daily lives of affected children and their families. In addition, clinical data collection continued to refine estimates of incidence, outcome and outcome predictors for each functional type of cardiomyopathy (i.e., dilated, hypertrophic, restrictive, and mixed type). In the current funding cycle, study aims were expanded through collaboration with the Pediatric Heart Transplant Study Group to examine the effect of cardiac transplantation on the clinical course of cardiomyopathy, as well as to establish the longitudinal course of functional status and its relationship to clinical events and outcomes, including heart transplantation. Finally, for the first time since the establishment of the Registry biological specimens (blood and cardiac tissue) are being collected to begin to investigate the relationship of genetic and viral markers with clinical and functional outcomes.

Analyses of the PCMR database have resulted in important findings regarding the incidence of cardiomyopathy in children, determination of the etiology of these cardiomyopathies, precise estimates of mortality and cardiac transplantation outcomes, determinants of outcomes for children with dilated and hypertrophic cardiomyopathy, the clinical course of children with cardiomyopathies and dystrophinopathies, and historical patterns of therapy. This paper reviews prominent PCMR findings and describes the current ongoing research studies associated with the PCMR.

Section snippets

Methods

The PCMR design and implementation are presented in detail elsewhere [1]. In brief, patients aged 18 years or less diagnosed with cardiomyopathy at participating centers are eligible for inclusion in the PCMR. Patients with specific secondary causes of myocardial abnormalities were excluded, including but not limited to potential causes of myocardial hypertrophy such as congenital heart disease and exposure to drugs known to cause cardiac hypertrophy (Table 1). Each case is classified according

Conclusions

The PCMR is currently in the thirteenth year of funding by the NHLBI and contains detailed clinical information on over 3000 cases. Important discoveries to date include the estimation of incidence of pediatric cardiomyopathy in the United States, identification of predictors of clinical outcomes for children with dilated or hypertrophic cardiomyopathy, and factors associated with the establishment of etiology for pediatric cardiomyopathy. Results of analyses regarding children with

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An LV posterior wall or septal thickness at end-diastole Z-score of 4–6 standard deviations above the normal mean for body-surface area has been suggested as possible HCM and a Z-score of 7 or more as definite HCM in children [20]. In the prior PCMR studies, a posterior wall thickness of >2 standard deviations above the normal mean for body-surface area was used as an inclusion criteria [19]. For the current study, the investigators were more selective requiring an LV posterior wall or septal thickness Z-score >3 to meet HCM inclusion criteria (certainly above the normal range for most children) (Table 2).
Cardiomyopathies are a rare cause of pediatric heart disease, but they are one of the leading causes of heart failure admissions, sudden death, and need for heart transplant in childhood. Reports from the Pediatric Cardiomyopathy Registry (PCMR) have shown that almost 40% of children presenting with symptomatic cardiomyopathy either die or undergo heart transplant within 2 years of presentation. Little is known regarding circulating biomarkers as predictors of outcome in pediatric cardiomyopathy.
The Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) study is a multi-center prospective study conducted by the PCMR investigators to identify serum biomarkers for predicting outcome in children with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Patients < 21 years of age with either DCM or HCM were eligible. Those with DCM were enrolled into cohorts based on time from cardiomyopathy diagnosis: categorized as new onset or chronic. Clinical endpoints included sudden death and progressive heart failure.
There were 288 children diagnosed at a mean age of 7.2 ± 6.3 years who enrolled in the PCM Biomarkers Study at a median time from diagnosis to enrollment of 1.9 years. There were 80 children enrolled in the new onset DCM cohort, defined as diagnosis at or 12 months prior to enrollment. The median age at diagnosis for the new onset DCM was 1.7 years and median time from diagnosis to enrollment was 0.1 years. There were 141 children enrolled with either chronic DCM or chronic HCM, defined as children ≥2 years from diagnosis to enrollment. Among children with chronic cardiomyopathy, median age at diagnosis was 3.4 years and median time from diagnosis to enrollment was 4.8 years.
The PCM Biomarkers study is evaluating the predictive value of serum biomarkers to aid in the prognosis and management of children with DCM and HCM. The results will provide valuable information where data are lacking in children.
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Primary (confined to the heart muscle) or secondary (extrinsic in origin) cardiomyopathies, whether genetic, idiopathic, or acquired account for the second largest group of pediatric heart failure patients, with an incidence of 1.3/100,000 [13]. PCM, a heterogeneous disease with a strong genetic component in the vast majority of diagnoses, is classified by its phenotypic expression [11]. The phenotypic expressions and respective incidence of pediatric cardiomyopathies include dilated (48%), hypertrophic (30%), noncompaction (9%), restrictive (< 5%), and arrhythmogenic ventricular cardiomyopathy (5%) [14].
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^☆: Supported by the National Heart Lung and Blood Institute (HL53392) and the Children's Cardiomyopathy Foundation.

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The Pediatric Cardiomyopathy Registry: 1995–2007☆

Abstract

Introduction

Section snippets

Methods

Conclusions

J Pediatr

Design and implementation of the North American Pediatric Cardiomyopathy Registry

Am Heart J

Incidence, causes, and outcomes of dilated cardiomyopathy in children

Jama

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

N Engl J Med

Epidemiology of idiopathic cardiomyopathies in children and adolescents. A nationwide study in Finland

Am J Epidemiol