Background Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM. Methods and Results The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age <22 years and DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using Cox proportional hazards modeling and classification and regression tree analysis. Of the 127 patients, 28 (22%) had disease progression during the 18-month follow-up. Multivariable analysis identified older age at diagnosis (hazard ratio=1.14 per year; P<0.001), larger left ventricular (LV) end-diastolic M-mode dimension z-score (hazard ratio=1.49; P<0.001), and lower septal peak systolic tissue Doppler velocity z-score (hazard ratio=0.81; P=0.01) as independent predictors of disease progression. Classification and regression tree analysis stratified patients at risk of disease progression with 89% sensitivity and 94% specificity based on LV end-diastolic M-mode dimension z-score ≥7.7, LV ejection fraction <39%, LV inflow propagation velocity (color M-mode) z-score <-0.28, and age at diagnosis ≥8.5 months. Conclusions In children with chronic stable DCM, a combination of diagnosis after late infancy and echocardiographic parameters of larger LV size and systolic and diastolic function predicted disease progression.

Although parvovirus B19 (PVB19) currently is the most common cause of viral myocarditis, limited pediatric data exist. Whereas other viruses infect cardiomyocytes, PVB19 targets coronary endothelium, leading to myocardial ischemia and dysfunction. A retrospective review investigated patients with polymerase chain reaction (PCR)-verified PVB19 myocarditis at Texas Children's Hospital and Arkansas Children's Hospital (January 2005 to August 2008). The primary end points of the study were transplant-free survival and circulatory collapse (death, mechanical support, or transplantation). For the 19 patients identified (age, 6 months to 15 years), the most common presenting symptoms were respiratory and gastrointestinal. At admission, all the patients demonstrated ventricular dysfunction requiring inotropic support (median ejection fraction, 24 %; median left ventricle end-diastolic diameter [LVEDD] z-score, 4.6). Whereas T-wave abnormalities were common, ST elevation was evident in five patients (two died and three required transplantation). Serum B-type natrietic peptide was elevated in all 12 patients tested (range, 348-8,058 pg/ml), and troponin I was high in 7 of 9 patients (range, 0.04-14.5 ng/ml). Of the 15 patients with circulatory collapse, nine received mechanical support, eight underwent successful transplantation, and five died. Only six patients (32 %) experienced transplant-free survival, and five patients had full recovery of function at discharge. In the transplant-free survival group, ST changes on presenting electrocardiography were less likely (p = 0.03), and the admission LVEDD z-score tended to be lower (3.3 vs 5.6; p = 0.08). In children, PVB19 myocarditis causes significant mortality and morbidity. Although mechanical intervention can support patients in the initial stage of decompensated heart failure, patients with PVB19 myocarditis often demonstrate persistent dysfunction requiring medical therapy and transplantation.

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ObjectiveImmunosuppressant therapy plays a pivotal role in transplant success and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to exhibit significant pharmacological interpatient and intrapatient variability. This variability necessitates the collection of serial trough concentrations to ensure that the drug remains within therapeutic range. The objective of this study was to build a population pharmacokinetic (PK) model and use it to determine the minimum number of trough samples needed to guide the prediction of an individual’s future concentrations.Design, setting and patientsRetrospective data from 48 children who received tacrolimus as inpatients at Primary Children’s Hospital in Salt Lake City, Utah were included in the study. Data were collected within the first 6 weeks after heart transplant.Outcome measuresData analysis used population PK modelling techniques in NONMEM. Predictive ability of the model was determined using median prediction error (MPE, a measure of bias) and median absolute prediction error (MAPE, a measure of accuracy). Of the 48 children in the study, 30 were used in the model building dataset, and 18 in the model validation dataset.ResultsConcentrations ranged between 1.5 and 37.7 μg/L across all collected data, with only 40% of those concentrations falling within the targeted concentration range (12 to 16 μg/L). The final population PK model contained the impact of age (on volume), creatinine clearance (on elimination rate) and fluconazole use (on elimination rate) as covariates. Our analysis demonstrated that as few as three concentrations could be used to predict future concentrations, with negligible bias (MPE (95% CI)=0.10% (−2.9% to 3.7%)) and good accuracy (MAPE (95% CI)=24.1% (19.7% to 27.7%)).ConclusionsThe use of PK in dose guidance has the potential to provide significant benefits to clinical care, including dose optimisation during the early stages of therapy, and the potential to limit the need for frequent drug monitoring.

PA resuscitation is effective at restoring flow to the affected lung resulting in improved diameter of the PA, lung growth, and resolution of symptoms. PA resuscitation should be considered in all children with DOPA, including those beyond infancy.

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Antibody-mediated rejection is a major clinical challenge that limits graft survival. Various modalities of treatment have been reported in small studies in paediatric heart recipients. A novel approach is to use complement-inhibiting agents, such as eculizumab, which inhibits cleavage of C5 to C5a thereby limiting the formation of membrane attack complex and terminal complement-mediated injury of tissue-bound antibodies. This medical modality of treatment has theoretical advantages but the collective experience in its use in the solid organ transplant community remains small. We add to this experience by combining 14 cases from 6 paediatric heart centres in this descriptive study.