Echocardiographic characteristics in Fontan patients before the onset of protein-losing enteropathy or plastic bronchitis.

BACKGROUND: It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein-losing enteropathy (PLE) or plastic bronchitis (PB). DESIGN: In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow-up questionnaires were completed by 105 patients a median of 5.3 (1.5-8.5) years later to evaluate whether one of the complications had occurred since the examinations. RESULTS: A total of 91 patients never developed PLE or PB ("non-PLE/PB"); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with "present PLE/PB" when examined. Six "future PLE/PB" patients developed those complications later on and were identified on follow-up. The "future PLE/PB" patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1-0.5) m/s vs 0.3 (0.1-1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0-0.2) m/s vs 0.2 (0.0-0.6) m/s, P = .02) than the "non-PLE/PB" group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8-0.9) m/s vs 0.8 (0.6-0.9) m/s, (P = .01)) even before the onset of PLE or PB. CONCLUSION: An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB.

An Early Glenn Operation May be Associated with the Later Occurrence of Protein-Losing Enteropathy in Fontan Patients : Association of Early Glenn and Failing Fontan.

Protein-losing enteropathy (PLE) and plastic bronchitis (PB) are major causes of long-term mortality after Fontan operation. The objective of this study was to determine early clinical risk factors before the onset of PLE and PB. In a cohort study, 106 Fontan patients between 2005 and 2013 were examined. A median of 5.3 (1.5-8.5) years later, follow-up questionnaires were used to group the patients in a PLE or PB group (n = 14) and a non-PLE/PB group (n = 92). Prevalence of PLE was 9.4% (n = 10) and of PB 3.8% (n = 4). At follow-up, five patients (4.7%) died of PLE or PB. Median age at death was 6.2 years (IQR 10.5, 95% CI 5.3-23.4). We observed no significant group differences in gender distribution (p = 0.73), ventricular morphology (p = 0.87), surgical technique (p = 0.64), conduit fenestration (p = 0.34), age at Fontan operation (p = 0.54), and need for diuretics (p = 0.56). Hypoplastic left heart syndrome was more frequent in the PLE/PB group 50 vs. 22.8% (p = 0.03) OR 3.4 (95% CI 1.1-10.8). The modified Glenn procedure was performed at a median age of 4 months (IQR 4.0) in the PLE/PB group versus 8 months (IQR 8.0) in the non-PLE/PB group (p = 0.01). The early Glenn procedure and hypoplastic left heart syndrome may be associated with the development of PLE and PB.

Predictors of health-related quality of life in children with chronic heart disease.

OBJECTIVE: Chronic paediatric heart disease is often associated with residual symptoms, persisting functional restrictions, and late sequelae for psychosocial development. It is, therefore, increasingly important to evaluate the health-related quality of life of children and adolescents with chronic heart disease. The aim of this study was to determine medical and socio-demographic variables affecting health-related quality of life in school-aged children and adolescents with chronic heart disease. Patients and methods The Pediatric Cardiac Quality of Life Inventory was administered to 375 children and adolescents and 386 parental caregivers. Medical information was obtained from the charts. The socio-demographic information was provided by the patients and caregivers. RESULTS: Greater disease severity, low school attendance, current cardiac medication, current parental employment, uncertain or limited prognosis, history of connection to a heart-lung machine, number of nights spent in a hospital, and need for treatment in a paediatric aftercare clinic independently contributed to lower health-related quality of life (self-report: R2=0.41; proxy-report: R2=0.46). High correlations between self-reports and parent-proxy reports indicated concordance regarding the evaluation of a child's health-related quality of life. CONCLUSIONS: Beyond medical treatment, integration into school is important to increase health-related quality of life in children and adolescents surviving with chronic heart disease. Regular screening of health-related quality of life is recommended to identify patients with special needs.

Clinical and in vitro effect of dornase alfa in mechanically ventilated pediatric non-cystic fibrosis patients with atelectases.

INTRODUCTION: At present no evidence-based medical treatment for persistent atelectasis in pediatric non-cystic fibrosis (CF) patients is available. METHOD: To evaluate the use of intratracheally instilled recombinant human deoxyribonuclease (rhDNase) in intubated and ventilated pediatric patients, we performed a single-center observational study on 46 pediatric intensive care patients who had received intratracheal DNase. Patients were classified, according to radiologic findings of atelectasis (group 1) or infiltrates. As controls we examined a historical control group of 17 patients with atelectasis after cardiac surgery, who had been treated with NaCl 0.9% and matched for age and diagnosis with 21 patients from group 1 (subgroup 1a). Radiologic improvement and inflammatory markers in both serum and tracheal aspirates were measured. RESULTS: In group 1, 35 patients had 51 atelectases/dystelectases episodes at baseline. 67 % of patients showed radiologic signs of improvement after 24h treatment with rhDNase. In subgroup 1a, 16 patients had complete resolution of atelectases and minimal change in dystelectases after a treatment of 24 hours rhDNase, compared with the control group of 17 patients, who had 7 atelectases and 10 dystelectases at baseline and an improvement in only 1 out of 17 (6 %) patients after 24h. CONCLUSION: Intratracheal instillation of rhDNase is an effective adjunct to conservative therapy of atelectases in children. Further randomized controlled prospective studies are necessary.

DNA quantification and fragmentation in sputum after inhalation of recombinant human deoxyribonuclease.

BACKGROUND: Inhaled rhDNase may improve sputum viscosity and mucociliary clearance by cleavage of extracellular DNA derived for instance from dead leukocytes in purulent, highly viscous patient sputum. METHODS: Here we established a method to quantify rhDNase-mediated DNA fragmentation in sputum using gel electrophoresis. Sputum of Pseudomonas aeruginosa colonized cystic fibrosis (CF) patients with (CF+) or without (CF-) rhDNase treatment or mechanically ventilated non-CF patients receiving rhDNase (non-CF+) or not (non-CF-) was analyzed. DNA measurements from T-lymphocytes served as controls. Absolute DNA content and the relative quantity within eight molecular mass ranges (12000 to 200 bp) was determined by gel electrophoresis and densitometric analysis. RESULTS: Geometric mean sputum DNA concentrations were 0.41 mg/dl for CF- (n=54), 0.78 mg/dl for CF+ (n=60), 0.053 mg/dl for non-CF- (n=41) and 0.049 mg/dl for non-CF+ (n=28). Treatment with rhDNase resulted in fragmentation of DNA that was quantified by separation and densitometric analysis of the DNA on agarose gels. The new analysis method permits analysis of DNA cleavage with high accuracy. CONCLUSION: This new monitoring method facilitates DNA quantification and in vitro monitoring of rhDNase in sputum.

Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children.

Recombinant human deoxyribonuclease I (dornase alfa) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis. In a randomized, placebo-controlled, double-blind clinical study in 100 infants, we investigated whether the therapeutic use of dornase alfa can be extended to ventilated, fluid-restricted children to reduce reintubation rate, ventilation duration, pediatric intensive care unit (PICU) stay, and ventilation complications. While reintubation rates were similar for dornase alfa 7% vs. placebo 9% (odds ratio, 0.77; confidence interval, 0.11-4.9), the incidence of atelectasis (6 vs. 17, respectively; P-value 0.051), median ventilation time (2.2 vs. 3.4 days, respectively; P-value 0.043), median length of PICU stay (7 vs. 8 days, respectively; P-value 0.051), and mean costs (4,830 vs. 6,320, respectively) were lower in the dornase alfa group. No adverse effects were observed, even in critically ill patients. We found that dornase alfa was beneficial and safe. Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward, particularly when longer ventilation (>3 days) is expected in fluid-restricted children after cardiac surgery.

Fractally coated myocardial pacemaker leads in children.

UNLABELLED: We report our single centre experience with a new fractally coated myocardial unipolar lead (ELC35UP; Biotronik) in 96 pediatric patients (59% male, 41% female). Congenital heart disease (CHD) was associated in 89%. The age at implantation ranged between 2 days and 19 years, median for children with CHD 7.8 years, without CHD 4.7 years. Twenty percent of the children were younger than one year at implantation. Mean follow-up was 30 months (1-57 months). We compared our findings with a steroid eluting epicardial lead (CapSure EPI 4968; Medtronic) in 46 children with comparable age and sex-distribution. We found a lead survival of 87% after 57 months in the ELC35UP group (steroid lead: 87% after 129 months). Pacing energy thresholds were equal after 12 months (median 3.0 microjoules), but the sensing characteristics of the fractally coated lead was significantly superior to the steroid eluting lead with median R waves of 7.0 mV (steroid lead: 3.5 mV) after 12 months. Children with myocardial scar tissue requiring pacemaker therapy after surgery of CHD showed no differences in sensing and pacing thresholds in comparison to children with congenital rhythm disorders. The fractally coated screw-in lead offers technical advantages concerning the subxiphoidal implantation procedure. CONCLUSION: Fractally coated ventricular screw-in leads represent a feasible alternative to the common steroid eluting leads- especially in children requiring pacemaker therapy after surgery for CHD.

Formation of three-dimensional fetal myocardial tissue cultures from rat for long-term cultivation.

Three-dimensional cardiomyocyte cultures offer new possibilities for the analysis of cardiac cell differentiation, spatial cellular arrangement, and time-specific gene expression in a tissue-like environment. We present a new method for generating homogenous and robust cardiomyocyte tissue cultures with good long-term viability. Ventricular heart cells prepared from fetal rats at embryonic day 13 were cultured in a scaffold-free two-step process. To optimize the cell culture model, several digestion protocols and culture conditions were tested. After digestion of fetal cardiac ventricles, the resultant cell suspension of isolated cardiocytes was shaken to initialize cell aggregate formation. In the second step, these three-dimensional cell aggregates were transferred onto a microporous membrane to allow further microstructure formation. Autonomously beating cultures possessed more than 25 cell layers and a homogenous distribution of cardiomyocytes without central necrosis after 8 weeks in vitro. The cardiomyocytes showed contractile elements, desmosomes, and gap junctions analyzed by immunohistochemistry and electron microscopy. The beat frequency could be modulated by adrenergic agonist and antagonist. Adenoviral green fluorescent protein transfer into cardiomyocytes was possible and highly effective. This three-dimensional tissue model proved to be useful for studying cell-cell interactions and cell differentiation processes in a three-dimensional cell arrangement.

Hypoplasia of the left heart with discordant ventriculoarterial connections.

We report the rare combination of a severely hypoplastic left ventricle and discordant ventriculoarterial connections, with associated subpulmonary obstruction of the left ventricular outflow tract. The long tortuous arterial duct originated at an acute angle from the aorta, suggesting that the subpulmonary obstruction developed early in fetal life. Residual flow via the hypoplastic left ventricle to the pulmonary circulation after insertion of an aortopulmonary shunt resulted in haemodynamic deterioration, which was instantly reversed by closing the pulmonary trunk.