Auscultation While Standing: A Basic and Reliable Method to Rule Out a Pathologic Heart Murmur in Children.

PURPOSE: The distinction between physiologic (innocent) and pathologic (organic) heart murmurs is not always easy in routine practice, leading too often to unnecessary cardiology referrals and expensive investigations. We aimed to test the hypothesis that the complete disappearance of murmur on standing can exclude cardiac disease in children. METHODS: From January 2014 to January 2015, we prospectively included 194 consecutive children aged 2 to 18 years who were referred for heart murmur evaluation to pediatric cardiologists at 2 French medical centers. Heart murmur characteristics while supine and then while standing were recorded, and an echo-cardiogram was performed. RESULTS: Overall, 30 (15%) of the 194 children had a pathologic heart murmur as determined by an abnormal echocardiogram. Among the 100 children (51%) who had a murmur that was present while they were supine but completely disappeared when they stood up, only 2 had a pathologic murmur, and just 1 of them needed further evaluation. Complete disappearance of the heart murmur on standing therefore excluded a pathologic murmur with a high positive predictive value of 98% and specificity of 93%, albeit with a lower sensitivity of 60%. CONCLUSIONS: Disappearance of a heart murmur on standing is a reliable clinical tool for ruling out pathologic heart murmurs in children aged 2 years and older. This basic clinical assessment would avoid many unnecessary referrals to cardiologists.

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.

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 patient's age at the time of diagnosis. No patient died or developed DCM, and pacemaker-related complications were few.

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.

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.

Long-term evolution of stents implanted in branch pulmonary arteries.

BACKGROUND: Branch pulmonary artery stenosis complicates the management of congenital heart diseases. Surgical branch pulmonary artery angioplasty is associated with a high reintervention rate. As an alternative, percutaneous or intraoperative branch pulmonary artery stents have been implanted to improve efficiency, but long-term evaluations are limited. AIM: To describe the long-term evolution of branch pulmonary artery stents. METHODS: We conducted a retrospective cohort study at Tours University Hospital. All stents implanted by surgery or catheterization in branch pulmonary arteries with a minimum follow-up of 12 months and at least one catheterization control were included. The primary endpoint combined cardiovascular mortality, surgical or percutaneous reintervention for stent complication or new stent implantation. RESULTS: Between 2007 and 2017, 76 stents in 51 patients were included (62 stents implanted by surgery, 14 by catheterization). At implantation, the patients' mean age and weight were 4.7years (interquartile range 4.2years) and 17.3kg (interquartile range 11.0kg), respectively. Mean branch pulmonary artery minimum diameter was 4.1±2.1mm (mean Z-score-4.9±2.9), and mean initial stent diameter was 9.1±3.1mm. During a follow-up of 5.3years (range 0-11.2 years), freedom from primary endpoint was 86.8% (95% confidence interval 79.6-94.8%) at 1 year, 71.5% (95% confidence interval 61.9-82.7%) at 5years and 69.6% (95% confidence interval 59.6-81.2%) at 10 years. We did not identify any factors associated with major adverse cardiovascular events. Among stents without major adverse cardiovascular events, the mean branch pulmonary artery diameter Z-score at last evaluation had increased by +4.8±3.2 compared with the initial diameter (P<0.001). After stent implantation, a median of 2 re-expansions were performed for each stent (range 0-7). CONCLUSIONS: Stent implantation should offer a good long-term solution for branch pulmonary artery stenosis, although iterative re-expansions are required.

Perforation of the atretic pulmonary valve using chronic total occlusion (CTO) wire and coronary microcatheter.

BACKGROUND AND OBJECTIVE: Chronic total occlusion (CTO) guidewire have been recently reported as an alternative to radiofrequency for perforating atretic pulmonary valve. Since procedure failures or perforation of the right ventricle still occurred with CTO, we tried to enhance the stability, steering, and pushability of the wire using a microcatheter in order to improve the safety and efficacy of the procedure. METHODS: We performed pulmonary valve perforation with CTO guidewire and microcatheter in five consecutive newborns with pulmonary atresia with intact ventricular septum (PA-IVS) under fluoroscopic and echocardiographic control. RESULTS: The valve was easily perforated at the first attempt for all patients. After perforation, the microcatheter positioned in the main pulmonary artery allowed the exchange of the CTO guidewire for a more flexible wire, avoiding lesion and facilitating manipulation in the distal pulmonary branch arteries. The pulmonary valve was then dilated with balloons of increasing size as usually performed. We did not experience any procedural or early complications. Blalock-Taussig shunt was performed in 2 children because of a persistent cyanosis, 4 and 10 days after perforation. CONCLUSIONS: The combined use of a CTO guide and a microcatheter appears to be a safe and reliable technique for perforating the pulmonary valve of newborns with PA-IVS. Further procedures with this approach are needed to confirm this first experience.

Immediate and midterm results of balloon angioplasty for recurrent aortic coarctation in children aged<1 year.

BACKGROUND: Several publications have considered results of percutaneous angioplasty for aortic recoarctation, but none focused on procedures performed in children aged<1 year. AIMS: To describe the immediate and midterm results of balloon angioplasty for recoarctation before the age of 1 year, and to define the factors that might influence outcome. METHODS: We retrospectively reviewed data from 20 consecutive children undergoing percutaneous dilatation for aortic recoarctation before the age of 1 year in the University Hospitals of Tours and Nantes. RESULTS: In all patients except one, dilatation improved the median recoarctation diameter Z-score from -5.5 (range -10.6 to -2.5) to -2.8 (range -4.3 to 0.7) (P<0.001), and reduced the median peak systolic gradient from 33mmHg (range 20 to 60mmHg) to 21mmHg (range 6 to 50mmHg) (P<0.001). There was no procedure-induced mortality and no acute intimal flap or long-term aneurysm. Three patients experienced a transient femoral artery thrombosis, one of whom had a transient ischemic stroke. Eight children (40%) needed reintervention for further recoarctation (new surgery [n=4] or new dilatation [n=4]). A smaller balloon size was significantly associated with the risk of reintervention: balloon to recoarctation diameter ratio 2.0 (range 1.3 to 3.3) vs. 2.7 (range 2.1 to 4.5) (P=0.05); balloon to descending aorta ratio 0.8 (range 0.7 to 1.2) vs. 1.0 (range 0.9 to 1.3) (P<0.05). CONCLUSIONS: In this study, percutaneous balloon angioplasty for recoarctation in young infants aged<1 year improved aortic isthmus diameter with a low incidence of adverse event. However, the rate of further intervention is high, and is associated with a smaller balloon size.

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.

Intraoperative Stenting of Pulmonary Artery Stenosis in Children With Congenital Heart Disease.

BACKGROUND: Branch pulmonary artery (BPA) stenosis is frequently associated with congenital heart disease. Management of BPA stenosis is challenging for surgeons due to a high rate of recurrence. The purpose of this study was to assess the results of intraoperative pulmonary artery stenting associated with or without surgical angioplasty. METHODS: We included 33 children from our center between January 2008 and July 2014. Patients had pulmonary atresia with ventricular septal defect (13), tetralogy of Fallot (10), troncus arteriosus (4), double outlet right ventricle (2), and single left or right ventricle (4). A total of 44 balloon-expandable stents (mean diameter, 9.5 mm; range, 4 to 16 mm) were deployed in left or right PA under direct visualization, without the use of fluoroscopy, after branch angioplasty for 28 of them (64%). The mean age at surgery was 4.3 ± 4.3 years (range, 6 days to 15 years) and the mean weight was 14.3 ± 11.9 kg (range, 2.8 to 63 kg). RESULTS: Postoperative mortality was 9% (3 patients), but only 1 death was related to the stenting procedure. Twenty-five patients underwent angiographic control after a mean follow-up of 22 months after surgery. All stents were well positioned. The mean stented BPA Z-score increased from -2.6 ± 1.8 to -0.4 ± 1.6 (p < 0.0001). Eleven patients experienced intrastent proliferation (44%). Among them, 2 patients required a reoperation for severe intrastent stenosis, whereas the 9 others had mild intrastent neointimal proliferation, which was successfully managed by balloon expansion. CONCLUSIONS: Intraoperative stenting of BPA is a safe and effective option to treat BPA stenosis and prevent recurrence.

Unusual Outcome of a Right Ventricular Rhabdomyoma in an Infant.

Rhabdomyomas are the most common benign cardiac tumors. They may often be associated with tuberous sclerosis. In many cases, cardiac rhabdomyomas undergo spontaneous regression. Here, we report the unusual case of an infant with a large nonobstructive right ventricular rhabdomyoma at birth and at four months of age, which subsequently caused severe right ventricle outflow tract obstruction at six months of age, prompting surgery to remove the tumor. Close monitoring should be done in infants with large nonobstructive cardiac rhabdomyomas.

Is Seprafilm valuable in infant cardiac redo procedures?

BACKGROUND: Morbidity 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. METHODS: Seventy-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. RESULTS: In 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. CONCLUSION: Our 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.

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.

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.

Significant persistent ductus arteriosus in infants less or equal to 6 kg: percutaneous closure or surgery?

BACKGROUND: Percutaneous closure of large persistent ductus arteriosus using the Amplatzer duct occluder is an alternative to surgery. However, this device is not recommended in infants weighing less than 6 kg. AIM: To evaluate the safety and effectiveness of this procedure in low-body-weight infants. METHODS: We reviewed retrospectively data for infants weighing less or equal to 6 kg who underwent percutaneous closure of significant persistent ductus arteriosus using the Amplatzer duct occluder in France between 1998 and 2007. RESULTS: Data for 58 patients (mean weight: 5 kg, range: 3.4-6; mean age: 5.5 months, range: 2.1-15.3) were reviewed. Mean angiographic persistent ductus arteriosus minimal diameter was 3.7 mm (range: 1-7.5). Implantation of the Amplatzer duct occluder was successful in 89.7% of cases. In six (10.3%) patients, the device was not implanted because it would have led to significant aortic obstruction. One procedure-related death occurred in a 4 kg infant (1.7%). Major and minor complications occurred in 6.9 and 31.0% of patients, respectively. Persistent ductus arteriosus diameter greater than 3.7 mm, type C (tubular shape) and diameter/patient weight ratio greater than 0.91 were significantly associated with an unsuccessful procedure and/or major complications. During a median 10-month follow-up, no late device embolization occurred. CONCLUSIONS: Although percutaneous closure of significant persistent ductus arteriosus with the Amplatzer duct occluder is effective in low-body-weight infants, the level and severity of complications indicate surgery as first-line treatment, at least until further studies are done to assess the safety and effectiveness of the new Amplatzer duct occluder II in low-body-weight infants.

Unusual hemodynamic changes in an infant with a restrictive ventricular septal defect.

A 7-month-old asymptomatic infant was known to have a restrictive membranous ventricular septal defect partially closed by an aneurysm of the membranous septum. At 13 months of age, he developed unexpected pulmonary hypertension, with no clinical sign of cardiac failure. Cardiac catheterization assessed the pulmonary artery pressure at a systemic level with significant left-to-right shunt. After surgical closure, the pulmonary arterial pressure decreased by 50%. We suspect an enlargement of the ventricular septal defect caused by the rupture of the aneurysm of the membranous septum-a rare complication.