Article

Competing Risks for Death and Cardiac Transplantation in Children With Dilated Cardiomyopathy Results From the Pediatric Cardiomyopathy Registry

Department of Pediatrics (D820), Miller School of Medicine, University of Miami, P.O. Box 016820, Miami, FL 33101, USA.
Circulation (Impact Factor: 14.95). 08/2011; 124(7):814-23. DOI: 10.1161/CIRCULATIONAHA.110.973826
Source: PubMed

ABSTRACT Pediatric dilated cardiomyopathy (DCM) is the leading indication for heart transplantation after 1 year of age. Risk factors by etiology at clinical presentation have not been determined separately for death and transplantation in population-based studies. Competing risks analysis may inform patient prioritization for transplantation listing.
The Pediatric Cardiomyopathy Registry enrolled 1731 children diagnosed with DCM from 1990 to 2007. Etiologic, demographic, and echocardiographic data collected at diagnosis were analyzed with competing risks methods stratified by DCM etiology to identify predictors of death and transplantation. For idiopathic DCM (n=1192), diagnosis after 6 years of age, congestive heart failure, and lower left ventricular (LV) fractional shortening z score were independently associated with both death and transplantation equally. In contrast, increased LV end-diastolic dimension z score was associated only with transplantation, whereas lower height-for-age z score was associated only with death. For neuromuscular disease (n=139), lower LV fractional shortening was associated equally with both end points, but increased LV end-diastolic dimension was associated only with transplantation. The risks of death and transplantation were increased equally for older age at diagnosis, congestive heart failure, and increased LV end-diastolic dimension among those with myocarditis (n=272) and for congestive heart failure and decreased LV fractional shortening among those with familial DCM (n=79).
Risk factors for death and transplantation in children varied by DCM etiology. For idiopathic DCM, increased LV end-diastolic dimension was associated with increased transplantation risk but not mortality. Conversely, short stature was significantly related to death but not transplantation. These findings may present an opportunity to improve the transplantation selection algorithm.

0 Followers
 · 
135 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.
    Clinics (São Paulo, Brazil) 01/2014; 69(Suppl 1):55-72. · 1.42 Impact Factor
  • Source
    BMJ Clinical Research 08/2014; 349:g5060. DOI:10.1136/bmj.g5060 · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Progressive heart failure leading to transplantation or death is common in pediatric dilated cardiomyopathy (DCM), and treatment options are limited. Select children with DCM have improved after cardiac resynchronization therapy (CRT), but predicting response is challenging. Nonetheless, considering the frequency of death or transplantation in this population, identifying any candidate would be valuable. Classic-pattern dyssynchrony (CPD) identifies mechanical dyssynchrony patterns consistent with underlying electrical activation delays and strongly predicts CRT response in adult DCM but has not been evaluated in pediatric DCM. The aim of this study was to test the hypothesis that CPD is present in a subgroup of patients with pediatric DCM and is associated with activation delays. Methods Fifty-nine subjects with pediatric DCM (left ventricular end-diastolic diameter Z score > 2 and left ventricular ejection fraction < 40%) who underwent echocardiography with a functional protocol with apical images optimized for two-dimensional speckle-tracking strain analysis (EchoPAC) were retrospectively analyzed for CPD. Electrocardiograms were evaluated for activation delays (prolonged QRS duration and strict criteria for left bundle branch block [LBBB]). Forty control subjects with no cardiac disease and good imaging widows were also analyzed. Results The mean age was 5.4 years (range, 1 day to 20 years); idiopathic DCM was most common (57%). Severe cardiomyopathy was present in 75% (end-diastolic diameter Z score > 4.6 and left ventricular ejection fraction < 32%). CPD was identified in seven subjects (12%), and prolonged QRS durations were present in 13 (22%), but only two subjects met strict criteria for LBBB. Six of seven subjects in the CPD group had prolonged QRS durations, and two of seven had LBBB. No control subjects had CPD. The CPD analysis was highly feasible and reproducible. Conclusions In this severely affected cohort, the small CPD subgroup is potentially important because their progressive disease may respond to CRT. CPD is associated with activation delays, although not necessarily strict LBBB. This has important potential implications for prospective evaluation of CRT in this disease.
    Journal of the American Society of Echocardiography 09/2014; 27(9). DOI:10.1016/j.echo.2014.06.014 · 3.99 Impact Factor

Full-text (2 Sources)

Download
22 Downloads
Available from
Jun 1, 2014