TMEM70 deficiency: long-term outcome of 48 patients.

OBJECTIVES: TMEM70 deficiency is the most common nuclear-encoded defect affecting the ATP synthase. In this multicentre retrospective study we characterise the natural history of the disease, treatment and outcome in 48 patients with mutations in TMEM70. Eleven centers from eight European countries, Turkey and Israel participated. RESULTS: All 27 Roma and eight non-Roma patients were homozygous for the common mutation c.317-2A > G. Five patients were compound heterozygotes for the common mutation and mutations c.470 T > A, c.628A > C, c.118_119insGT or c.251delC. Six Arab Muslims and two Turkish patients were homozygous for mutations c.238C > T, c.316 + 1G > T, c.336 T > A, c.578_579delCA, c.535C > T, c.359delC. Age of onset was neonatal in 41 patients, infantile in six cases and two years in one child. The most frequent symptoms at onset were poor feeding, hypotonia, lethargy, respiratory and heart failure, accompanied by lactic acidosis, 3-methylglutaconic aciduria and hyperammonaemia. Symptoms further included: developmental delay (98%), hypotonia (95%), faltering growth (94%), short stature (89%), non-progressive cardiomyopathy (89%), microcephaly (71%), facial dysmorphism (66%), hypospadias (50% of the males), persistent pulmonary hypertension of the newborn (22%) and Wolff-Parkinson-White syndrome (13%). One or more acute metabolic crises occurred in 24 surviving children, frequently followed by developmental regression. Hyperammonaemic episodes responded well to infusion with glucose and lipid emulsion, and ammonia scavengers or haemodiafiltration. Ten-year survival was 63%, importantly for prognostication, no child died after the age of five years. CONCLUSION: TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.

Noninvasive positive pressure ventilation in critically ill children with cardiac disease.

Noninvasive ventilation is effective in respiratory failure from various etiologies. This study aimed to analyze the efficacy of noninvasive positive pressure ventilation (NPPV) in pediatric cardiac patients. NPPV was used (1) as an alternative means of respiratory support in patients with hypoxemic or hypercarbic respiratory failure or with signs of respiratory distress that were considered to require intubation; or (2) as a preventive measure in patients with high risk for extubation failure. Between 2008 and 2011, there were 107 episodes of NPPV use in 82 patients. Their median age was 57 days (range 1 day to 18 years), and weight was 4.1 kg (range 1.7-68). Within the first hour of NPPV, partial pressure of carbon dioxide/fraction of inspired oxygen (PaO2/FiO2) was significantly increased, and arterial pCO2, and respiratory rate were decreased. This decrease in respiratory rate and increase in PaO 2/FiO2 continued during the first 24 h of therapy, and pCO2 was decreased during the first 6 h. In 59.8% of cases, NPPV was successfully used without the need for tracheal intubation. The Aristotle Basic Complexity score, presence of infection, residual cardiac defect, and pH <7.36 in the first hour were independent predictors of NPPV failure. We conclude that NPPV improved oxygenation and decreased respiratory effort in pediatric cardiac patients, 59.8% of whom eventually did not receive intubation. A high-complexity surgical score, presence of infection, residual cardiac defect, and pH <7.36 in the first hour are predictors of NPPV failure, which occurs in most patients >24 h after the onset of therapy.

Thrombus obstructing the right ventricle outflow tract in a neonate with methylenetetrahydrofolate reductase 677TT genotype.

At her first day of life, a neonate presented with severe cyanosis and a mass obstructing the right ventricle outflow tract. Prostagladin E1 was necessary to provide pulmonary blood flow. The mass was removed using extracorporeal bypass surgery; the right ventricle was dilated, and the pulmonary valve leaflets were damaged. Sternal closure was delayed because of bleeding and poor cardiac performance. Histology demonstrated that the mass was a mixed thrombus. Investigation revealed homozygous 677TT genotype of the methylenetetrahydrofolate reductase. In conclusion, a life-threatening thrombotic event such as an intracardiac thrombus obstructing the right ventricle outflow tract can occur in a neonatal age. Since the event can be a result of a combination of acquired and congenital thrombogenic risk factors, an extensive screening including DNA-based mutation analysis should be performed.

The use of high-frequency jet ventilation for removal of obstructing casts in patients with plastic bronchitis.

OBJECTIVE: To describe improved cast removal with short periods of high-frequency jet ventilation (HFJV) in patients with single ventricle physiology. DESIGN: Case report. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Two patients with plastic bronchitis during prolonged stay in a intensive care unit after a Fontan-type operation. INTERVENTIONS: Short periods of HFJV. MAIN RESULTS: Plastic bronchitis with lower airway obstruction developed in two intubated patients during intensive care stay after the Fontan operation. Mucolytics and suctioning were not effective in controlling symptoms. Urgent bronchoscopy was considered a high-risk procedure for the first patient and was not available for the second. Cast removal was achieved with short periods of HFJV and subsequent suctioning. CONCLUSIONS: The use of short-term HFJV resulted in resolution of the airway obstruction in intubated patients with plastic bronchitis.

Transatlantic medical consultation and second opinion in pediatric cardiology has benefit past patient care: A case study in videoconferencing.

BACKGROUND: Telemedicine is a rapidly evolving form of modern information and communication technology used to deliver clinical services and educational activities. OBJECTIVE: The aim of this article is to report and analyze our experience with transatlantic consultation via videoconferencing in pediatric cardiology. METHODS: In February, 2013, videoconferencing project was launched between a medium-volume pediatric cardiac center in Bratislava, Slovakia and subspecialty experts from a high-volume pediatric cardiac program at The Children's Hospital of Philadelphia (CHOP), USA. During 1.5-2 hours videoconferences, 2-3 patients with similar complex clinical scenarios were presented to CHOP experts. The main goal of the project was consultation on individual patients to validate, alter or radically change clinical management plans. RESULTS: From February, 2013 to January, 2017, 25 videoconferences occurred and 73 cases were discussed. The median patient age was 52 months (range; 1 day-30 years). Forty-six discussed cases were outpatients, 21 patients were in the intensive care unit and 6 patients were discussed post mortem. Thirty-one CHOP experts from different subspecialties participated actively in patient consultations. The most frequent recommendations were related to single ventricle, pulmonary hypertension or heart failure patients and intervention in complex and/or rare cardiac diseases. Specialists from CHOP agreed completely with the original care plan in 16% of cases. In 52% cases, adjustments to original plan were suggested. Radical changes were recommended in 30% of cases. Receiving institution adopted recommendations to the patient care fully in 79% and partially in 13% of patients. CONCLUSIONS: Based on our 4-year experience we consider videoconferencing between medium-size pediatric cardiac center and subspecialty experts from a high-volume pediatric cardiac program a suitable form of medical consultations. Videoconferencing assists in clinical decision making for complex patient cases and serves as an effective educational tool to gain knowledge and experience "without borders."

Immune Abnormalities in Patients With Single Ventricle Circulation Precede the Fontan Procedure.

BACKGROUND: Immune abnormalities are common in Fontan patients with protein-losing enteropathy. Limited data exist on immune function of other patients with single ventricle circulation. METHODS: This prospective cohort study evaluated immunologic characteristics of children with single ventricle circulation from neonatal age up to early post-Fontan period. RESULTS: Low leukocyte counts were observed in half of the patients prior to bidirectional Glenn and Fontan surgery. Total lymphocyte counts were below normal range in 36% to 63% of patients across all groups except patients following Fontan procedure who had normal counts. Typical lymphocyte subpopulation patterns were (1) high counts of total and helper T lymphocytes (CD3+ and CD4+ cells), low B lymphocytes (CD19+ cells), and increased CD4/CD8 ratio in neonates and (2) low T lymphocytes (CD3+, CD4+, CD8+ cells) with high natural killer cells (CD16+) and B lymphocytes (CD19+ cells) in other groups. Low preoperative total lymphocyte counts were associated with longer intensive care unit stay in patients after bidirectional Glenn and Fontan procedure ( P = .03 and P = .01, respectively) and low leukocyte counts with higher incidence of pleural effusions and chylothorax after Fontan procedure ( P = .005 and P = .002, respectively). CONCLUSIONS: Single ventricle patients display several immunological abnormalities. Beyond the neonatal age, an immune pattern includes CD3+, CD4+, CD8+ lymphopenia, and CD16+ and CD19+ lymphocytosis. B-cell lymphocytosis compensates T-cell lymphopenia, producing normal total lymphocyte counts in patients early after Fontan surgery. Low preoperative total lymphocyte counts may be associated with longer postoperative intensive care unit stay in patients with bidirectional Glenn and Fontan procedure and leukopenia with pleural effusions in Fontan patients.

Natural history of newborn with borderline small left heart without interatrial communication.

A patient with a borderline small left heart requires difficult clinical decision making during prenatal and neonatal periods. This report describes the unusual natural history of a newborn with prenatally diagnosed hypoplastic left heart structures and early spontaneous postnatal closure of the interatrial communication. Initial deterioration from pulmonary edema and low-cardiac output improved with postnatal intensive care. During the seventh week of life, aortic coarctation was diagnosed and the infant underwent uneventful surgical repair. Despite transient clinical deterioration, early spontaneous closure of the interatrial communication in a newborn with borderline small left heart could be associated with gradual hemodynamic adaptation to postnatal biventricular circulation.

Fístula arterial coronaria gigante: diagnóstico prenatal y manifestación neonatal / Giant coronary artery fistula: prenatal diagnosis, newborn manifestation

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A comparison of Blalock-Taussig shunts with and without closure of the ductus arteriosus in neonates with pulmonary atresia.

BACKGROUND: The question of whether to close the patent ductus arteriosus when performing primary modified Blalock-Taussig (MBT) shunt surgery in neonates is still not clearly answered. The aim of this report was to compare the results of closure versus nonclosure of the patent ductus arteriosus during MBT shunt surgery in neonates with pulmonary atresia. METHODS: This retrospective study included neonates with pulmonary atresia who underwent primary MBT shunt surgery through a sternotomy approach at our institution between January 1997 and October 2010. Mortality, resuscitation events, and the need for reintervention within the first 48 postoperative hours were studied as primary outcomes. RESULTS: Sixty-two neonates (mean age 6.9±5.5 days) underwent a MBT procedure. The arterial duct was closed surgically in 31 patients, and left open in 31 patients. Compared with patients in whom the PDA was left open, patients with a surgically closed arterial duct had a higher incidence of resuscitation events (29.0% versus 0%, p=0.0012), reinterventions (35.5% versus 3.2%, p=0.0013), and higher early hospital mortality (9.7% versus 0%, p=0.038). Time to extubation and length of hospital stay did not differ between the two groups (p=0.16 and p=0.73, respectively). A trend toward a higher maximum vasoactive-inotropic score in the group with a closed duct was observed (median 13.5 versus 10, p=0.10). CONCLUSIONS: In newborns with pulmonary atresia, ductal closure during MBT shunt procedure is associated with increased incidence of resuscitation events, need for reintervention, and increased mortality during the early postoperative period.

Non-invasive positive pressure ventilation for bilateral diaphragm paralysis after pediatric cardiac surgery.

We present the case histories of two children having respiratory failure due to bilateral diaphragm paralysis after cardiac surgery. In both children non-invasive positive pressure ventilation alleviated respiratory distress, improved gas exchange, and prevented the need for endotracheal intubation. Following unilateral recovery of diaphragmatic function both children were successfully weaned from non-invasive positive pressure ventilation.

Amiodarone as a first-line therapy for postoperative junctional ectopic tachycardia.

BACKGROUND: Postoperative junctional ectopic tachycardia is a potentially life-threatening arrhythmia that is often resistant to conventional antiarrhythmic drugs. Amiodarone was suggested to be an adequate treatment; however, data regarding its efficacy and safety are limited. This study evaluated the efficacy of amiodarone in the first-line treatment of postoperative junctional ectopic tachycardia and assessed factors associated with failure of amiodarone therapy. METHODS: The study included 40 pediatric cardiosurgical patients with postoperative junctional ectopic tachycardia. Intravenous amiodarone in 2-mg/kg boluses and, if necessary, as continuous infusion (10 to 15 mug/kg/min), were used as the first-line therapy. Restoration of sinus rhythm or slowing of junctional ectopic tachycardia to a rate that allowed atrial or atrioventricular sequential pacing was considered as efficacy of therapy. RESULTS: Amiodarone was effective in 18 patients (45%). Sinus rhythm was achieved in 7, and heart rate decreased in 11 patients from 180 (range, 173 to 200) to 142 (range, 133-155) beats/min (p < 0.0001) and allowed effective pacing with atrioventricular synchrony. Higher arteriovenous oxygen saturation difference (p = 0.007) and lower body temperature (p = 0.02) were associated with failure of amiodarone therapy. CONCLUSIONS: Amiodarone as the first-line treatment was effective in almost half of the patients with postoperative junctional ectopic tachycardia. Higher arteriovenous oxygen saturation difference and lower body temperature were associated with failure of amiodarone therapy, and their presence may suggest more aggressive initial approach consisting of amiodarone combined with hypothermia.

Disturbances of coagulation in neonates with functionally univentricular physiology prior to the first stage of surgical reconstruction.

BACKGROUND: Altered levels of coagulation factors are reported in patients with functionally univentricular physiology before and following the second and third stages of reconstructive surgery. The aims of our study were to determine if such abnormalities are also present in newborns with this physiology prior to the first stage of surgical treatment. PATIENTS AND METHODS: We studied 20 neonates with functionally univentricular physiology admitted to the Children's Cardiac Centre in Slovakia, using 20 healthy neonates as age-matched controls. Demographic characteristics, and concentration of liver enzymes, serum albumin, and complete blood count, did not differ between the two groups. Concentrations of Factor II, V, VII, VIII, Protein C, Protein S and Antithrombin were compared between the groups, and assessed as variable factors for coagulation. RESULTS: In those with functionally univentricular physiology, procoagulation Factor II (p < 0.001), VII (p < 0.001), VIII (p < 0.01), anticoagulation Protein C (p < 0.001), Protein S (p < 0.001) and Antitrombin III (p < 0.001) all were present in significantly lower values compared with findings in the control group. D-dimer (p < 0.0001) and Fibrin Degradation Products (p < 0.0001) were present at significantly higher levels, but the concentration of plasminogen was significantly lower (p < 0.0001). The activated partial thromboplastin time (p < 0.012), and the prothrombin time (p < 0.0001), was significantly prolonged in those with functionally univentricular physiology compared with their controls. CONCLUSION: The presence of abnormal coagulation factors, markers of thrombolysis in the plasma, and increased risk of bleeding, suggests activation of haemostasis, and consumption of factors responsible for coagulation, in those with functionally univentricular physiology. The question arises whether the reported abnormalities are predictive of the known abnormalities of coagulation occurring during the second and third stages of surgical repair for patients with functionally univentricular hearts.