Treating Children With Idiopathic Dilated Cardiomyopathy (from the Pediatric Cardiomyopathy Registry)

doi:10.1016/j.amjcard.2009.03.033

The American Journal of Cardiology

Volume 104, Issue 2, 15 July 2009, Pages 281-286

https://doi.org/10.1016/j.amjcard.2009.03.033 Get rights and content

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 from 1990 to 1995 (n = 350) and from 2000 to 2006 (n = 219). At diagnosis, 73% had symptomatic heart failure (HF), and 7% had ≥1 family member with IDC. Anti-HF medications were most commonly prescribed initially. Anti-HF medication use was similar across the 2 periods (84% and 87%, respectively), as was angiotensin-converting enzyme inhibitor 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 was 4% to 18% over the 2 periods. Treatments for pediatric IDC have changed little over the previous 25 years. Anti-HF 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 angiotensin-converting enzyme inhibitors without echocardiographic evidence of advanced disease. In conclusion, therapeutic clinical trials are strongly indicated because practice variation is substantial and medical outcomes in these children have not improved in the previous several decades.

Section snippets

Methods

The purpose of the PCMR is to identify epidemiologic characteristics and clinical course of selected cardiomyopathies in children and to promote development of cause-specific prevention and treatment strategies. The design of the PCMR is described elsewhere.¹² The present analysis is based on the retrospective cohort of the PCMR, for which detailed therapeutic data were obtained by standardized chart abstraction on 920 children with cardiomyopathy who presented to a pediatric cardiologist from

Results

The PCMR enrolled 920 children with cardiomyopathy diagnosed from 1990 to 1995, of which of 350 had pure IDC or familial isolated IDC (Table 1). Echocardiographic findings from month of presentation were consistent with IDC. Use of selected medications in this patient group was compared with that in a group of 219 children with pure IDC diagnosed from 2000 to 2006 for whom medication data, other than anti-HF therapy, were collected. Anti-HF therapy data for children diagnosed from 2000 to 2006

Discussion

Childhood IDC is a rare but highly debilitating disease of multiple causes with profound morbidity and mortality.5, 8, 19 The disease most often affects very young children, and indeed, presentation during infancy was noted in 43% of the children reported in this study. The 1- and 5-year rates for death or transplantation for children with IDC enrolled in the PCMR are 39% and 53%, respectively, illustrating the relative inadequacy of current medical therapy.⁵ In this study, we found little

Acknowledgment

The authors thank Meena Doshi, MS, for assistance with statistical analyses.

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Cited by (47)

30- and 60-Day Readmission Rates for Children With Heart Failure in the United States
2024, JACC: Heart Failure
Studies on readmission for pediatric heart failure (HF) patients is sparse.
This study evaluated 30- and 60-day readmission rates in pediatric HF patients from 2010 to 2019.
The authors used data from the Nationwide Readmission Database to evaluate trends in 30- and 60-day hospital readmissions among pediatric patients with HF and compare them with adults with HF. Readmissions were also stratified by sex, diagnosis, neighborhood income, and hospital volume.
There were 84,731 hospital admissions for HF. Compared with children without HF, those with HF were older, had Medicare/Medicaid insurance, and resided in micropolitan areas and low-income neighborhoods. The 30- (19.5% vs 3.1%) and 60-day (27.5% vs 4.3%) all-cause readmission rates were higher for children with HF compared with those without HF. Compared with children without HF, lengths of stay, deaths, and costs related to their readmission were higher for children readmitted with HF (P < 0.05 for all). There was no significant decline in pediatric HF-related 30- or 60- day readmissions during the study period overall, or for those with congenital heart disease (P > 0.05), unlike adult HF readmissions (P < 0.01). Infants were at highest risk, and readmission rates for teenagers are rising.
The 30- and 60-day readmission rates for pediatric patients with HF in the current era is high (∼20% and 30%, respectively). Unlike adult HF, pediatric HF readmission rates have not declined. Pediatric HF patients readmitted to the hospital have higher death rates and greater resource utilization than patients without HF. National measures to decrease readmissions for pediatric patients with HF is warranted.
Survival Without Cardiac Transplantation Among Children With Dilated Cardiomyopathy
2017, Journal of the American College of Cardiology
Citation Excerpt :
Another possibility is that changing medical management of these children has improved transplant-free survival. In the past decade, more children have been treated early with beta-blockers and angiotensin-converting enzyme inhibitors for extended periods of time (25,42,43). In addition, the improved recognition and management of acute heart failure at initial diagnosis or at exacerbation with enhanced intensive care unit–level care may have led to better transplant-free survival in the more recent decade.
Studies of children with dilated cardiomyopathy (DCM) have suggested that improved survival has been primarily due to utilization of heart transplantation.
This study sought to determine transplant-free survival for these children over 20 years and identify the clinical characteristics at diagnosis that predicted death.
Children <18 years of age with some type of DCM enrolled in the Pediatric Cardiomyopathy Registry were divided by year of diagnosis into an early cohort (1990 to 1999) and a late cohort (2000 to 2009). Competing risks and multivariable modeling were used to estimate the cumulative incidence of death, transplant, and echocardiographic normalization by cohort and to identify the factors associated with death.
Of 1,953 children, 1,199 were in the early cohort and 754 were in the late cohort. Most children in both cohorts had idiopathic DCM (64% vs. 63%, respectively). Median age (1.6 vs. 1.7 years), left ventricular end-diastolic z-scores (+4.2 vs. +4.2), and left ventricular fractional shortening (16% vs. 17%) at diagnosis were similar between cohorts. Although the rates of echocardiographic normalization (30% and 27%) and heart transplantation (24% and 24%) were similar, the death rate was higher in the early cohort than in the late cohort (18% vs. 9%; p = 0.04). Being in the early cohort (hazard ratio: 1.4; 95% confidence interval: 1.04 to 1.9; p = 0.03) independently predicted death.
Children with DCM have improved survival in the more recent era. This appears to be associated with factors other than heart transplantation, which was equally prevalent in both eras. (Pediatric Cardiomyopathy Registry [PCMR]; NCT00005391)
Readmissions for Heart Failure in Children
2016, Journal of Pediatrics
Citation Excerpt :
Interestingly, the use of ACE/ARBs was somewhat decreasing. Data from the Pediatric Cardiomyopathy Registry have shown that patients with better ventricular function are less likely to be prescribed an ACE inhibitor or a beta-blocker at discharge.20 The data from this cohort did not demonstrate any differences in the incidence of prescribing ACE inhibitors or beta-blockers, based on markers of critical illness, although echocardiographic information was not available in the PHIS and, if present, may clarify this finding.
To assess the frequency of inpatient 30-day readmission for heart failure in children with cardiomyopathy discharged after an admission for heart failure and the impact of discharge pharmacotherapy on readmissions.
The Pediatric Health Information System Database was queried for patients ≤18 years of age with an International Classification of Diseases, Ninth Revision code for heart failure (428.xx) or cardiomyopathy (425.xx) discharged from 2004 to 2013. Patients were excluded if they had congenital heart disease, expired on the initial admission, or underwent cardiac surgery. Patient admission characteristics were documented and discharge medications were captured. Frequency of 30-day readmission for heart failure was identified, and mixed effects multivariable logistic regression analysis was performed to determine factors significant for readmission.
A total of 2386 patients met study criteria (52.1% male, median age 8.1 years [IQR 1.2-14.6 years]). Vasoactive medications were used in 70.3% of patients on initial admission, the most common of which was milrinone (62.8%). Angiotensin converting enzyme inhibitors and beta-blockers were given at discharge to 67.4% and 35.9%, respectively. Frequency of 30-day readmission for heart failure was 12.9%. Duration of milrinone or beta-blocker use at discharge and institutional heart failure patient volume were associated with a greater odds of 30-day readmission, whereas mechanical ventilation on initial admission was associated with decreased odds of readmission.
Pediatric patients with cardiomyopathy and heart failure have a high frequency of heart failure-related 30-day readmission. Outpatient pharmacotherapy at discharge does not appear to influence readmission.
The link between pediatric heart failure and mitochondrial lipids
2014, Current Therapeutic Research - Clinical and Experimental
Dysregulation of cardiolipin biosynthesis in pediatric heart failure
2014, Journal of Molecular and Cellular Cardiology
Citation Excerpt :
Evidence-based medical therapy for adults with heart failure (HF) is well established and has improved clinical outcomes [9]. In contrast, modern medical regimens have not significantly improved outcomes in children with HF over those from the 1970s digoxin and diuretic era therapy [5,10,11]. While primary disorders of mitochondrial respiration are a known cause of myocardial dysfunction in children and adults, secondary mitochondrial dysfunction may be a down-stream effect contributing to heart failure [12–15].
Cardiolipin, a unique phospholipid in the inner mitochondrial membrane, is critical for optimal mitochondrial function. CL abnormalities have been demonstrated in the failing rodent and adult human heart. The aim of this study was to determine whether abnormalities in CL content and the CL biosynthesis and remodeling pathways are present in pediatric idiopathic dilated cardiomyopathy (IDC).
A cross-sectional analysis of myocardial tissue from 119 IDC and non-failing (NF) control samples was performed. Electrospray ionizing mass spectrometry was used to measure total CL and CL species content in LV tissue. RT-PCR was employed to measure gene expression of the enzymes in the CL biosynthesis and remodeling pathways in both the adult and pediatric heart. Significantly lower total and (18:2)₄CL (the beneficial species) content was demonstrated in myocardium from pediatric patients with IDC compared to NF controls. Analysis of mitochondrial gene transcripts was used to demonstrate that there is no decrease in mitochondrial content. Expression of two biosynthesis enzymes and one remodeling enzyme was significantly lower in pediatric IDC compared to NF controls. Expression of two phospholipases involved in CL degradation were also altered, one up- and one down-regulated. Except for one remodeling enzyme, these changes are unique from those in the failing adult heart.
Similar to what has been seen in adults and in a rat model of IDC, total and (18:2)₄CL are lower in pediatric IDC. Unique CL species profiles are seen in heart tissue from children with IDC compared to adults. Differences in CL biosynthesis and remodeling enzyme expression likely explain the differences in CL profiles observed in IDC and implicate unique age-related mechanisms of disease.
QRS prolongation is strongly associated with life-threatening ventricular arrhythmias in children with dilated cardiomyopathy
2013, Journal of Heart and Lung Transplantation
The incidence of sudden death in children with dilated cardiomyopathy has been estimated at < 1% annually. This number, however, may underestimate the incidence of life-threatening arrhythmias. The objective of this study was to assess the incidence of and identify risk factors for life-threatening arrhythmias in children with dilated cardiomyopathy.
We conducted a retrospective record review of 183 children with dilated cardiomyopathy treated at a single center between 2000 and 2011. Life-threatening arrhythmia was defined as any ventricular arrhythmia that resulted in syncope or hypotension and required medical intervention. Risk factors for life-threatening arrhythmias were identified with univariate analyses. A prediction model was constructed with multivariate logistic regression and receiver operating characteristic curves.
Nineteen patients experienced life-threatening arrhythmias, representing an annualized rate of 4.9%. Outpatient life-threatening arrhythmias occurred at a rate of 2.2% per year. Predictors of outpatient life-threatening arrhythmias were longer QRS duration (p = 0.003) and increased left ventricular posterior wall (LVPWd) thickness (p = 0.03). Only QRS duration remained significant in multivariate logistic regression (odds ratio, 1.8 for every unit increase in z-score; 95% CI, 1.01–1.9; p = 0.04). For all life-threatening arrhythmias, prolonged QRS duration was the only significant risk factor in multivariate logistic regression (odds ratio, 1.5; 95% CI, 1.1–2.2; p = 0.02).
In children with dilated cardiomyopathy, as QRS duration increases, so too does the risk of life-threatening arrhythmias. Life-threatening arrhythmias occurred at an annual rate of 5%, which was much higher than the previously reported rate of sudden cardiac death in this population.

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: This work was supported by Grant R01 HL53392 from the National Heart, Lung, and Blood Institute (Department of Health and Human Services), Bethesda, Maryland, and the Children's Cardiomyopathy Foundation.

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CardiomyopathyTreating Children With Idiopathic Dilated Cardiomyopathy (from the Pediatric Cardiomyopathy Registry)

Section snippets

Methods

Results

Discussion

Acknowledgment

Am J Cardiol

Am Heart J

Prog Pediatr Cardiol

Am Heart J

Prog Pediatr Cardiol

J Heart Lung Transplant

J Am Coll Cardiol

J Pediatr

Prog Pediatr Cardiol

Cardiomyopathy
Treating Children With Idiopathic Dilated Cardiomyopathy (from the Pediatric Cardiomyopathy Registry)