Pediatric Dilated Cardiomyopathy Patients Research Articles

Disturbed Desmoglein-2 in the intercalated disc of pediatric patients with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) leads to disturbed contraction and force transduction, and is associated with substantial mortality in all age groups. Involvement of a disrupted composition of the intercalated disc (ID) has been reported. However, in children, little is established about such subcellular changes during disease, because of the pathological mix-up with the ongoing cardiac maturation. This leaves maladaptive remodeling often undetected. We aimed at illustrating subcellular alterations in children diagnosed with DCM compared to age-matched controls, focusing on ID proteins known to be crucially stable under healthy conditions and destabilized during cardiac injury in adults. Left ventricular or septal pediatric specimens were collected from 7 individuals diagnosed with DCM (age: 23 weeks in utero to 8 weeks postnatal) and age-matched controls that died of non-cardiovascular cause. We determined the amount of fibrosis and localization of ID proteins by immunohistochemistry. In pediatric DCM, most ID proteins follow similar spatiotemporal changes in localization as in controls. However, although no mutations were found, the signal of the desmosomal protein Desmoglein-2 was reduced in all pediatric DCM specimens, but not in controls or adult DCM patients. Endocardial and transmural fibrosis was increased in all pediatric DCM patients compared to age-matched controls. Composition of the ID in pediatric DCM patients is similar to controls, except for the localization of Desmoglein-2 and presence of severe fibrosis. This suggests that the architecture of desmosomes is already disturbed in the early stages of DCM. These findings contribute to the understanding of pediatric DCM.

Etiology and prognosis of 183 cases with primary dilated cardiomyopathy

Objective To explore the etiology, clinical features and outcomes predictors of pediatric dilated cardiomyopathy(DCM). Methods The clinical findings and follow-up data of 183 pediatric DCM patients who were diagnosed during Jan.2008 to Dec.2012 were analyzed. Results In the 183 patients, the cause of 24 cases(13.1%)was known; but the etiology of 132 follow-up cases remain unknown, 85 were male(64.0%) and 47 were female(36.0%); 33 cases(25.0%) recovered, 62 cases(47.0%)died, and 37 cases(28.0%) remained the same.The median age of onset was 8 months(ranged from 1 day to 15 years). The onset age of the patients who had recovered was younger than the dead(P<0.001) and the unchanged patients(P=0.008). For the dead cases, the heart function on diagnosis was worse than the cured(P<0.001) and the unchanged patients(P=0.015); the left ventricular ejection fraction(LVEF) and the left ventricular fractional shortening(LVFS) detected by ultrasonic cardiogram were significantly lower than those of the cured(P=0.006, 0.009) and the unchanged (P=0.013, 0.006); the cases with mode-rate and serious mitral regurgitation(MR) were also more than the other groups(P=0.003, 0.004); The cases in the unchanged group were less than those of the cured group and the dead group whose serum concentration of cardiac troponin I was≥0.10 μg/L(P=0.002, 0.004). For the 159 cases with the unknown cause, 1-year survival rate was 67% and 5-year survival rate was 46%.By multivariable analysis, LVFS[hazard ratios(HR)0.890, 95% confidence interval (CI)0.836-0.948, P<0.001], moderate and serious MR[HR 3.580, 95%CI 2.030-6.315, P<0.001], malignant ventricular arrhythmia[HR 2.062, 95%CI 1.009-4.213, P=0.047], abnormal Q wave[HR 4.044, 95%CI 1.851-8.832, P<0.001]were associated with increased risk of death. Conclusions Twenty-five percent pediatric idiopathic DCM patients with the unknown cause recovered after proper treatment, and nearly 50.0% patients died; 1-year survival rate was 67.0% and 5-year survival rate was 46.0%.Three months after onset, the patients whose left ventricular function improved obviously had a better outcome.Risk factors for death include LVFS, moderate and serious MR, malignant ventricular arrhythmia, abnormal Q wave. Key words: Dilated cardiomyopathy; Etiology; Outcomes; Child

Variability of M-Mode Versus Two-Dimensional Echocardiography Measurements in Children With Dilated Cardiomyopathy

M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1month later. These data were used to assess reproducibility and agreement between M-mode and 2D measurements. One hundred sixty-nine subjects were enrolled. M-mode had similar or greater reproducibility in both intrareader and interreader settings for LV dimensions, shortening fraction (SF), and most wall thicknesses. In contrast, 2D reproducibility was similar or better for nearly all variables in the interacquisition setting but not for SF. Interacquisition variability was approximately twice the intrareader variability. LV dimensions by either modality consistently had high reproducibility and had the highest agreement between modalities. In pediatric DCM patients, variability of linear echocardiographic assessment could be minimized by relying on a single reader and using a consistent method (M-mode or 2D) for serial measurements, preferably M-mode when SF is the primary variable of interest. Except for LV dimensions, M-mode and 2D values should not be used interchangeably due to poor agreement.

Autologous cellular cardiomyoplasty for pediatric dilated cardiomyopathy patients: New therapeutic option for children with failing heart?

Autologous cellular cardiomyoplasty for pediatric dilated cardiomyopathy patients: New therapeutic option for children with failing heart?

Abstract 4952: Differential Expression in the Determinants of Extracellular Matrix Remodeling in Pediatric and Adult Dilated Cardiomyopathy

Ventricular phenotype of idiopathic dilated cardiomyopathy (DCM) can appear similar in pediatric and adult patients, but a more aggressive clinical course often occurs with pediatric DCM. A structural underpinning of DCM is extracellular matrix changes, which are determined by a balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). This study tests the hypothesis that different MMP/TIMP profiles occur in pediatric and adult DCM patients. Left ventricular samples were taken from pediatric (age 12±4 yr; n=5) and adult (age 63±3 yr; n=11) patients during heart transplantation for DCM. Myocardial levels were quantified for all MMP classes: gelatinases (MMP-2, -9), collagenases (MMP-8, -13), lysins (MMP-7), membrane-type (MT1-MMP), and for all 4 known TIMPs. Patients with structural or ischemic etiologies of DCM were excluded. Compared to adults, MMP-8 levels increased by over 350% (Figure ), and MMP-7 and MT1-MMP levels (75±9% and 76±9%, respectively; p&lt;0.05) were lower in pediatric patients. In contrast, pediatric TIMP-1 levels were reduced by over 50% (Figure). Pediatric DCM patients manifest a robust increase in MMP-8, which degrades all components of the extracellular matrix, and a decrease in TIMP-1, which inhibits MMP-8. This heightened MMP-8/TIMP-1 ratio would favor aggressive matrix remodeling in pediatric DCM. Since MMP-8 is primarily expressed by macrophage cell lineage, a unique proteolytic program may exist in pediatric DCM. These distinct differences in determinants of myocardial matrix structure and function likely contribute to the more progressive nature of DCM in children.

Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation

ObjectivesWe studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation. BackgroundThe outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain. MethodsWe performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation. ResultsAt the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from “heart death” (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation. ConclusionsPediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM.