A. Chantepie

Maternal and fetal outcomes of pregnancy with Fontan circulation: A multicentric observational study

BACKGROUND Despite serious long-term sequel, women with Fontan palliation have reached childbearing age. However there is paucity of data on the pregnancy outcomes and management of this condition. We aimed to determine the maternal and fetal outcomes of pregnancy in women with Fontan palliation. METHODS This multicentric, retrospective study included women with Fontan circulation followed in 13 French specialized centers from January 2000 to June 2014. All pregnancies were reviewed, including miscarriages, abortions, premature and term births. We reviewed maternal and fetal outcomes. RESULTS Thirty-seven patients had 59 pregnancies. Mean age was 27 ± 5 years at first pregnancy. There were 16 miscarriages (27%) and 36 live births with 1 twin pregnancy. Cardiac events occurred in 6 (10%) pregnancies, with no maternal death. The most common cardiac complication was atrial arrhythmia, which occurred in 3 patients. Hematological complications including thromboembolic/hemorrhagic events (n=3/7) occurred in 5 women antepartum (n=2/3), and 4 women postpartum (n=1/4). Two of the 3 thromboembolic events occurred in patients without anticoagulation. There was a high incidence of prematurity (n=25/36, 69%). Anticoagulation was associated with adverse neonatal outcome (OR=10.0, 95% CI [1.5-91.4], p<0.01). After a median follow-up of 24 months, there was no significant worsening of clinical status and thromboembolic disease noted. CONCLUSIONS Pre-selected women can successfully complete pregnancy with Fontan circulation. There is an increase in cardiac and neonatal morbidity during pregnancy. Because thromboembolism could have a severe consequence on Fontan circulation, anticoagulation should be indicated during pregnancy and postpartum period.

Characteristics and long-term outcome of non-immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study

AIMS The natural history of congenital or childhood non-immune, isolated atrioventricular (AV) block is poorly defined. METHODS AND RESULTS We retrospectively studied 141 children with isolated, non-immune AV block diagnosed in utero, or up to 15 years of age, at 13 French medical centres, between 1980 and 2009. Patients with structural heart disease or maternal antibodies were excluded. Atrioventricular block was asymptomatic in 119 (84.4%) and complete in 100 (70.9%) patients. There was progression to complete AV block in 29/41 (70.7%) patients with incomplete AV block over 2.8 ± 3.4 years (1-155 months), but all patients with incomplete AV block may not have been included in the study. Narrow QRS complex was present in 18 of 26 patients (69.2%) with congenital, and 106 of 115 (92.2%) with childhood AV block. Pacemakers were implanted in 112 children (79.4%), during the first year of life in 18 (16.1%) and before 10 years of age in 90 (80.4%). The mean interval between diagnosis of AV block and pacemaker implants was 2.6 ± 3.9 years (0-300 months). The pacing indication was prophylactic in 70 children (62.5%). During a mean follow-up of 11.6 ± 6.7 years (1-32 years), no patient died or developed dilated cardiomyopathy (DCM). The long-term follow-up was uncomplicated in 127 children (90.1%). CONCLUSION In this large multicentre study, the long-term outcome of congenital or childhood non-immune, isolated AV block was favourable, regardless of the patients age at the time of diagnosis. No patient died or developed DCM, and pacemaker-related complications were few.

Outcome of coronary artery bypass grafting performed in young children

OBJECTIVES The long-term patency rate of coronary artery bypass grafting for which arterial grafts are used is known to be high in the pediatric population. However, this issue remains uncertain in children under 3 years of age. Here, we report the outcome in this specific population. METHODS From July 1988 to July 2007, 18 children less than 3 years of age (age at operation, 0.1-35 months; median, 4 months) underwent 20 coronary artery bypass graft operations using an arterial graft. Indications for bypass grafting were coronary artery complications related to the arterial switch operation for transposition of the great arteries in 12 patients (coronary obstruction in 8 patients, peroperative coronary anomalies precluding coronary transfer in 4 patients), congenital anomalies of the coronary arteries in 4 patients, and Kawasaki disease in 2 patients. RESULTS After a mean follow-up of 55 months (range, 1-176 months; median, 41 months), patency of 19 bypass grafts was assessed. One was occluded and 2 have necessitated a percutaneous procedure. Two patients died suddenly (1 with an occluded graft and 1 with a patent graft and hypertrophic myocardiopathy) 3.5 and 4.6 months, respectively, after bypass grafting. CONCLUSIONS Coronary artery bypass grafting should be considered as a possible alternative for coronary revascularization in young children. Although our series shows quite a good patency rate, this procedure remains a technical challenge and requires careful follow-up.

Barth syndrome in a female patient

BACKGROUND Barth syndrome (BTHS) is an X-linked recessive disorder characterized by cardiomyopathy, skeletal myopathy and cyclic neutropenia in male patients. It is caused by mutations in the TAZ gene coding for the tafazzin, a protein involved in the remodeling of cardiolipin. Loss of cardiolipin in the inner mitochondrial membrane results in respiratory chain dysfunction. No specific symptom has been identified in female carriers. CASE REPORT We report the first case of BTHS confirmed by TAZ gene analysis in a female patient. This girl experienced severe heart failure at 1-month of age. Echocardiography diagnosed dilated-hypokinetic and hypertrophic cardiomyopathy with noncompaction of the left ventricle. Initial metabolic screening was normal, except for a cyclic neutropenia. Respiratory chain analysis performed on skin fibroblasts revealed a decreased activity of complexes I, III and IV. Screening on a bloodspot showed abnormal monolysocardiolipin:cardiolipin ratio, later confirmed on cultured fibroblasts, indicative of BTHS. Genetic analyses finally confirmed the diagnosis of BTHS, by showing a large intragenic deletion of exons 1 through 5 in the TAZ gene. Cytogenetic analysis showed mosaicism for monosomy X and for a ring X chromosome with a large deletion of the long arm including the Xq28 region. The girl presented recurrent episodes of severe acute heart failure, progressive muscle weakness, and had a fatal septic shock at 3 years. CONCLUSION This case highlights that the diagnosis of BTHS should also be suspected in female patients presenting a phenotype similar to affected boys. In these cases, analysis of the monolysocardiolipin:cardiolipin ratio in bloodspots is a rapid and sensitive screening tool for BTHS. However clinical expression in a carrier female requires hemizygosity for the mutated allele of the TAZ gene, which supposes a rearrangement of the TAZ gene region on the other X chromosome.

Parental Electrocardiographic Screening Identifies a High Degree of Inheritance for Congenital and Childhood Nonimmune Isolated Atrioventricular Block

Background— The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. Methods and Results— A multicenter retrospective study (13 French referral centers, from 1980–2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0±6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001). A long PR interval was found in 18.5% of the parents but never in control subjects (P<0.0001). Complete or incomplete right bundle-branch block was observed in 39.2% of the parents and 1.5% of the control subjects (P<0.0001). Complete or incomplete left bundle-branch block was found in 15.4% of the parents and 3.1% of the control subjects (P<0.0006). Estimated heritability for isolated conduction disturbances was 91% (95% confidence interval, 80%–100%). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. Conclusions— ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.

Transient Hypertrophic Cardiomyopathy in Neonates After Acute Fetal Distress

We report three cases of transient myocardial hypertrophy, diagnosed by echocardiography, occurring between the second and seventh days of life in neonates with initially normal ventricular myocardial wall thickness. The three term neonates had perinatal injury with acute fetal distress. In all three cases electrocardiographic and biologic signs of myocardial ischemia were present. The first echocardiographic results showed abnormalities in systolic or diastolic left ventricular function, without hypertrophy of the walls. The hypertrophic cardiomyopathy (HCM) occurred between days 2 and 7 and affected first the interventricular septum and the free wall of the right ventricle. The left ventricular posterior wall subsequently became abnormal, resulting in severe overall myocardial hypertrophy, which finally disappeared in all three cases between 1 and 5 months of life. Such observations of early severe and transient HCM have not been previously reported. We believe it is a consequence of myocardial ischemia due to acute fetal distress. The prognosis of this type of HCM is good, in contrast to that of other primitive HCM occurring in neonates.

Bénéfices de l’insulinothérapie par pompe chez les enfants diabétiques de type 1

BACKGROUND The Diabetes Control and Complications Trial clearly demonstrated the benefits of blood glucose control, especially in children and adolescents, in the prevention of long-term complications of type 1 diabetes (T1D). This can be achieved with intensive insulin treatment with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII), also known as insulin pump. The aim of this study was to compare glycemic control of T1D children treated with either CSII or MDI. PATIENTS AND METHODS Thirty-eight T1D children treated with CSII were compared to 38 children treated with MDI, matched for age, gender, and duration of diabetes. Collected data, including daily doses of insulin in IU/kg/d, HbA1c levels, body mass index expressed in standard deviation/age, number of severe hypoglycemia episodes and of admissions related to T1D expressed in events/patient/year, were retrospectively collected every 3 months. RESULTS There was no difference between the 2 groups at baseline. During the 3 years of follow-up, patients treated with CSII had lower daily doses of insulin (0.78 ± 0.19 vs. 0.87 ± 0.22 IU/kg/d, p<0.05), significantly lower levels of HbA1c (7.5 ± 0.6 vs. 8.0 ± 1.3 %, p<0.05), and a decreased number of admissions related to T1D (0.07 ± 0.14 vs. 0.17 ± 0.22 events/patient/year, p<0.05) than children treated with MDI. In contrast, body mass index and number of severe hypoglycemic episodes did not differ between the two groups. No diabetic ketoacidosis episode was recorded in either group. CONCLUSION The results from this study suggest that treatment with CSII provided better metabolic control than treatment with MDI, in spite of lower daily doses of insulin and without increasing acute complications, in children with T1D.

Danon disease: intrafamilial phenotypic variability related to a novel LAMP-2 mutation.

Danon disease is an X-linked lysosomal disorder, characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation. We report a family with a novel mutation, in which the mother and her three sons were affected with various clinical presentations. A massive hypertrophy of the left ventricle was the predominant feature in the three male patients, with different degrees of severity of cardiac symptoms, from isolated palpitations to cardiac failure and sudden death. Muscle pain and weakness were also variable, but constantly associated with increased plasma CK levels. Finally, the male patients had variable degree of a mental retardation. The mother had an attenuated phenotype, limited to a mild hypertrophic cardiomyopathy with premature ventricular contractions diagnosed during her 40’s. Microscopy examination of skeletal muscle biopsy, performed in the youngest patient, demonstrated atrophic myofibers with intracytoplasmic vacuoles suggesting lysosomal glycogen storage disease. Immunohistochemistry analyses in muscle specimen showed no detectable Lysosomal-Associated Membrane Protein-2 (LAMP-2), in keeping with the diagnosis of Danon disease. However, a very low expression of a shortened LAMP-2 protein could be evidenced by Western-blot in the patient’s fibroblasts. Molecular investigations identified a novel splicing mutation (IVS6 + 1delG) in the LAMP-2 gene. This case report highlights the intrafamilial variability of Danon disease phenotype. In this case, morphological examination of muscle biopsy, showing lysosomal storage myopathy, and immunohistochemistry analyses can provide key elements for orienting etiologic investigations.

Association Between Tetralogy of Fallot and Tracheobronchial Branching Abnormalities: A New Clue for Pathogenesis?

Background In our practice, we noticed an increased frequency of tracheobronchial branching abnormalities (TBAs) in patients with tetralogy of Fallot (ToF). This study aimed to determine whether an association exists between congenital TBAs and ToF with or without pulmonary atresia. Methods and Results The frequency of TBAs on chest computed tomography was assessed in 55 patients with ToF without pulmonary atresia, 34 patients with ToF with pulmonary arteria, and 100 control patients. We then looked for a possible association between TBAs and pulmonary artery branch hypoplasia, the presence of major aortopulmonary collateral arteries, and the presence of the chromosome 22q11 deletion. TBAs were significantly more frequent in patients with ToF with or without pulmonary atresia than in the control group (any TBAs, 21% versus 2% [P<0.001]; bronchial situs anomalies, 6% versus 0% [P=0.002]; right tracheal bronchus, 4% versus 0% [P=0.04]; left eparterial bronchus, 8% versus 0% [P=0.005]); and tended to be more frequent in those with ToF without pulmonary atresia than in those with ToF with pulmonary atresia (any TBAs, 27% versus 12% [P=0.11]; left eparterial bronchus, 13% versus 0% [P=0.04]). TBAs were readily multiple (8 patients of 19 with TBA) and concerned essentially the upper lobes. TBAs were not associated with pulmonary branch hypoplasia, major aortopulmonary collateral arteries, or the chromosome 22q11 deletion. Conclusions We demonstrated a significantly increased frequency of tracheobronchial abnormalities in patients with ToF with or without pulmonary atresia compared with a control group. These results suggest an interaction between abnormalities in conotruncal septation and tracheobronchial branching and may provide a new clue to the pathogenesis of conotruncal heart diseases.

Is Seprafilm valuable in infant cardiac redo procedures

BackgroundMorbidity and mortality are higher for cardiac reoperations than first operation due to the presence of post-operative adhesions. We retrospectively evaluated the efficacy of the bioresorbable membrane Seprafilm® to prevent pericardial adhesions after cardiac surgery in a paediatric congenital heart disease population.MethodsSeventy-one children undergoing reoperations with sternotomy redo and cardiopulmonary bypass for congenital malformations were included. Twenty-nine of these patients were reoperated after previous application of Seprafilm® (treatment group). The duration of dissection, aortic cross clamping and total surgery were recorded. A tenacity score was established for each intervention from the surgeon’s description in the operating report.ResultsIn multivariate analysis, the duration of dissection and the tenacity score were lower in the treatment than control group (p < 0.01), independent of age and interval since preceding surgery.ConclusionOur results suggest that Seprafilm® is effective in reducing the post-operative adhesions associated with infant cardiac surgery. We recommend the use of Seprafilm® in paediatric cardiac surgery when staged surgical interventions are necessary.