A gene for Holt-Oram syndrome maps to the distal long arm of chromosome 12.

Holt-Oram syndrome (HOS) is an autosomal dominant condition of unknown origin characterized by congenital septal heart defects with associated malformations of the upper limbs (radial ray). Here, we report on the mapping of a gene causing HOS to the distal long arm of chromosome 12 (12q21-qter) by linkage analysis in nine informative families (Zmax = 6.81 at theta = 0 at the D12S354 locus). Also, multipoint linkage analysis places the HOS gene within the genetic interval between D12S84 and D12S79 (multipoint lod-score in log base 10 = 8.10). The mapping of a gene for HOS is, to our knowledge, the first chromosomal localization of a gene responsible for congenital septal heart defect in human. The characterization of the HOS gene will hopefully shed light on the molecular mechanisms that govern heart septation in the early stages of embryogenesis.

Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia.

Friedreich ataxia (FRDA) is a common autosomal recessive degenerative disease (1/50,000 live births) characterized by a progressive-gait and limb ataxia with lack of tendon reflexes in the legs, dysarthria and pyramidal weakness of the inferior limbs. Hypertrophic cardiomyopathy is observed in most FRDA patients. The gene associated with the disease has been mapped to chromosome 9q13 (ref. 3) and encodes a 210-amino-acid protein, frataxin. FRDA is caused primarily by a GAA repeat expansion within the first intron of the frataxin gene, which accounts for 98% of mutant alleles. The function of the protein is unknown, but an increased iron content has been reported in hearts of FRDA patients and in mitochondria of yeast strains carrying a deleted frataxin gene counterpart (YFH1), suggesting that frataxin plays a major role in regulating mitochondrial iron transport. Here, we report a deficient activity of the iron-sulphur (Fe-S) cluster-containing subunits of mitochondrial respiratory complexes I, II and III in the endomyocardial biopsy of two unrelated FRDA patients. Aconitase, an iron-sulphur protein involved in iron homeostasis, was found to be deficient as well. Moreover, disruption of the YFH1 gene resulted in multiple Fe-S-dependent enzyme deficiencies in yeast. The deficiency of Fe-S-dependent enzyme activities in both FRDA patients and yeast should be related to mitochondrial iron accumulation, especially as Fe-S proteins are remarkably sensitive to free radicals. Mutated frataxin triggers aconitase and mitochondrial Fe-S respiratory enzyme deficiency in FRDA, which should therefore be regarded as a mitochondrial disorder.

[Tropical endomyocardial fibrosis: Perspectives]. / Fibrose endomyocardique tropicale : perspectives.

Tropical endomyocardial fibrosis (FET) is a leading cause of heart failure and the most common restrictive cardiomyopathy worldwide. Extensive fibrosis of the ventricular endocardium causing architectural distortion, impaired filling and valvular insufficiency define the disease. Confined to peculiar and limited geographical areas, the aetiology remains blurred and it carries a grim prognosis. The changing burden reported recently in some endemic areas and the refinement of diagnostic tools have emphasized alternative routes for understanding and treatment of the disease.

CT angiography of the artery of Adamkiewicz with 64-section technology: first experience in children.

BACKGROUND AND PURPOSE: Preoperative localization of the artery of Adamkiewicz (AKA) may be useful in selected children in prevention of ischemic spinal complications of spinal or thoracoabdominal aortic surgery. The aim of our study was to investigate the ability of 64-section CT for assessing the AKA in children. MATERIALS AND METHODS: Forty children (mean age, 7.5 +/- 5 years) underwent thoracic imaging with a 64-section CT scanner after intravenous injection of 1.5 mL/kg of contrast agent. Volumetric reconstructions were obtained for every patient. Identification of the AKA was performed on the basis of continuity from the aorta to the anterior spinal artery with a characteristic hairpin turn. Identification of the AKA and determination of its origin and course were analyzed by 2 independent radiologists. RESULTS: The AKA was successfully visualized in 38 patients (95%). Twenty-seven (71.1%) AKAs originated on the left side, whereas 11 (28.9%) originated on the right side. It was seen to originate at the level of the left 5th intercostal artery in 1 patient, the left 8th in 4, the left 9th in 15, the left 10th in 5, the left 11th in 2, the right 8th in 2, the right 9th in 6, the right 10th in 2, and the right 12th in 1. CONCLUSION: Sixty-four-section CT angiography depicted the AKA in a very high percentage (95%) of children. The results of this study suggest that 64-section CT angiography is a viable noninvasive technique that could be an alternate to selective angiography for delineating the AKA.

[Percutaneous closure of veno-venous fistulae after total cavopulmonary derivation: a case report]. / Fermeture percutanée de fistules veino-veineuses après dérivation cavo-pulmonaire totale: à propos d'un cas.

The authors report the case of a boy with a complex congenital heart malformation with a dextro-isomerism or Ivemark's syndrome. After several palliative procedures, a total cavopulmonary derivation was performed at the age of 11 years with implantation of a fenestrated tube between the inferior vena cava and the right pulmonary artery. The fenestration was closed two years later. At about 15 years of age, progressive systemic desaturation was observed; cardiac catheterisation with angiography showed a large number of intra-hepatic veno-venous collaterals draining into a large left suprahepatic vein which drained into the right atrium connected to the systemic ventricle. The largest fistula was embolised with a 20 mm Amplatzer Duct Occluder and two others with 14 x 12 and 10 x 8 Amplatzer Duct Occluders. The saturation rose from 75% to 94%. After 6 months' follow-up, the child is asymptomatic and the systemic saturation is 90%.

[Anomalous left main coronary artery with an inter-aorto-pulmonary trajectory: diagnostic value of 64-slice CT scan with cardiac synchronisation]. / Anomalie de naissance du tronc coronaire gauche avec un trajet interaortopulmonaire: apport du scanner 64 coupes avec synchronisation cardiaque.

Anomalous left coronary artery arising from the right sinus with an inter-aorto-pulmonary trajectory is a classical cause of sudden death and myocardial ischaemia in young adults. The mechanism is compression of the coronary during physiological dilatation of the great arteries on exercise. The authors report the case of a 12 year old child who had syncope on effort preceded by angina due to this malformation. The CT scan with 3-D reconstruction confirmed the diagnosis and the interarterial trajectory of the left coronary artery and the anatomical relationships with the vessels at the base of the heart. Cardiac CT scan is the investigation of choice for diagnosis and preoperative work-up of congenital coronary anomalies. In the authors' experience, the investigation is performed systematically when an anomalous coronary artery is suspected, in addition to echocardiography and instead of conventional coronary angiography.

[Utilisation of gastric ring systems for pulmonary artery banding: an animal study]. / Utilisation d'un système de cerclage gastrique comme cerclage réglable de l'artère pulmonaire: une étude chez l'animal.

OBJECTIVES: Pulmonary artery banding is often required as a first palliative procedure in infants with congenital heart disease and high pulmonary blood flow or to retrain the left ventricle. The purpose of the study was to demonstrate the safety of a gastric banding system as an adjustable pulmonary artery banding in chronic implantation. METHODS: Five ewes underwent implantation of the banding system around the main pulmonary artery through a left thoracotomy. All had functional evaluation with progressive occlusion and opening of the device every two weeks for a total period of three months. Invasive pressure measurements in the right ventricle and aorta were carried out each time. RESULTS: Devices could be implanted easily. Progressive occlusion and re-opening were possible in all animals during each time point. All animals survived throughout the protocol. Retrieval of the device was achieved in all animals. In one, it was challenging because of the presence of a fibrotic reaction around the device. It died because of pulmonary artery perforation before the sacrifice. At autopsy, microscopic examination showed no signs of myocardial fibrosis. CONCLUSIONS: In animals, gastric banding system is a safe and effective implantable device to adjust pulmonary artery diameter over a prolonged period of time. This new device may be a valuable alternative to the repeated conventional pulmonary artery banding needed for ventricular retraining in humans.

[Mycoplasma pneumoniae myopericarditis in children]. / Myopéricardite à Mycoplasma pneumoniae chez l'enfant.

Mycoplasma pneumoniae myocarditis is a rare condition, potentially very serious and seldom described in children. It is classically attributed to direct invasion or to an indirect immunological mechanism. The authors report the case of a 10 year old boy with myopericarditis, proved by authentic seroconversion, complicating congenital mitro-aortic valvular disease. In this case, the spectacular response to steroid therapy was in favour of an indirect immunological causal mechanism of the left ventricular dysfunction and pericardial involvement.

[Use of covered stents to occlude extracardiac Fontan fenestration]. / Utilisation de stents couverts pour la fermeture des fenestrations extracardiaques des dérivations cavopulmonaires totales.

INTRODUCTION: A fenestration is usually surgically created to improve the post-operative course of patients undergoing total cavopulmonary connection. It, however, has a potentially deleterious effect on the long-term period. Closure of these fenestrations is usually performed by interventional catheterization. No device has been specially designed and closure of extracardiac fenestration, in particular, can be challenging. We report our experience in occlusion of such fenestrations using covered stents (Numed Inc). METHODS: From July 2005 to October 2005, we attempted to occlude extracardiac Fontan fenestration using CP covered stents in 4 consecutive patients. RESULTS: All patients had a successful occlusion of the fenestration. The procedure was performed from femoral or jugular vein respectively in three and one patient. Mean central venous pressure did not increase significantly (from 11.25 to 12.75 mmHg) whereas mean oxygen saturation increased significantly from 92% to 99% (p=0.0047). Abolition of shunt was obtained immediately after insertion of the covered stent in all patients. No early complications were observed. All patients were ambulatory the day after the procedure. CONCLUSION: The insertion of a covered stent inside the extracardiac Fontan conduit allowed the exclusion of the fenestration in all patients without the need of crossing the fenestration and with no early mortality or morbidity. Long-term follow-up are needed before considering the use of such device as the device of choice in that application.

[Spontaneous idiopathic chylopericardium in childhood]. / Chylopericarde idiopathique spontané de l'enfant.

Here we report a case of a primary idiopathic chylopericardium in a 13 years old child. Pericardial effusion was diagnosed because the child suffered chest pain and fatigue. Pericardial drainage was performed and 800mL of chylous fluid was evacuated. Extensive investigations were performed but no cause could be found. Thoracic CT scan, lymphoscintigraphy and MRI did not evidence any communication between the thoracic duct and pericardium. After 2 recurrences of pericardial effusion while the child was on a medium chain triglycerides regimen, it was decided to ligate the thoracic duct and to do a partial pericardectomy. The result was excellent with complete resolution of the pericardial effusion and no recurrence since 3 years.

[Development and evaluation of a prosthetic valved conduit dilated by percutaneous approach: experimental study in the lamb]. / Développement et évaluation d'un conduit prothétique muni d'une valve dilatable par voie percutanée: étude chez l'agneau.

This study was undertaken to develop a dilated valved conduit for reconstruction of the right ventricular outflow tract in the animal. The conduits were made by sewing a valved tube (Medtronic Inc) inside a vascular stent (Numed Inc). After preparation, they were inserted surgically in five lambs. The conduits were then dilated 6 weeks and 3 months after their implantation. Before sacrificing the animals at 3 months, a 22 mm valved stent was implanted percutaneously inside the surgical conduits. One animal died suddenly due to kinking of the conduit. Balloon dilatation was performed in the surviving animals. The first dilatation only had a modest impact on valvular function but it was much aggravated after the second dilatation. A valved stent was successfully inserted percutaneously. At sacrifice, all the conduits were completely engulfed in an intense fibrosis. In conclusion, a valved biological conduit for reconstruction of the right ventricular ejection tract has been developed and can be dilated sequentially to follow growth. The new product could have an important role to play in the management of congenital malformations involving the right ventricular outflow tract.

[Transcatheter exclusion of a giant aneurysm of the left pulmonary artery using covered stents]. / Exclusion d'un anévrisme géant de l'artère pulmonaire gauche par cathétérisme interventionnel: utilisation de stents couverts.

An 11 year-old boy with an Alagille syndrome was referred for an urgent echocardiography because of new onset of febrile hemoptysis. Follow-up in our institution to that point had shown severe hypoplastic pulmonary arteries. The diagnosis of tricuspid endocarditis complicated by pulmonary embolisms and aneurysm of the left pulmonary artery was done. Despite effective antiobiotics, the evolution was marked by rapid progression in size of the left pulmonary aneurysm. Since the surgery was not an option because of high risk of death, this aneurysm was treated by a trans-catheter technique using covered stents (CP stents, Numed Inc). Its exclusion allowed to stop its progression in size and to avoid its rupture.

[Multislice CT scan in congenital heart disease]. / Le scanner volumique dans les cardiopathies congénitales.

The management of congenital cardiovascular malformations is a diagnostic challenge. It requires accurate assessment of the intra- and extra-cardiac malformations. Three-dimensional imaging by the multislice CT scanner is now a routine investigation for congenital heart disease, complementary to echocardiography, and, increasingly, an alternative to conventional angiography. Three dimensional imaging is particularly useful in the diagnosis of complex congenital heart disease, in the preparation of complex investigations of interventional cardiac catheterisation and the postoperative evaluation of surgical repair. This report describes the different acquisition protocols adapted for children and illustrates the present role of volumic CT scanner in congenital heart disease by clinical examples of everyday clinical practice.

Transcatheter implantation of a bovine valve in pulmonary position: a lamb study.

BACKGROUND: Pulmonary regurgitation can lead to severe right ventricular dysfunction, which is a delicate postoperative problem in the long-term follow-up of patients who had surgery for congenital heart diseases. Clinical conditions of patients suffering from pulmonary valve incompetence are improved by valve replacement with a prosthetic valve. To date, the surgical approach is the only option to replace a pulmonary valve. We report the first experience of percutaneous pulmonary valve implantation. METHODS AND RESULTS: A fresh bovine jugular vein containing a native valve was sutured into a vascular stent and then cross-linked with a 0.6% glutaraldehyde solution for 36 hours. After being hand-crimped onto a balloon catheter, the device was inserted percutaneously according to standard stent-placing techniques. The valved stent was finally deployed in the position of the native pulmonary valve of the lamb. Hemodynamic evaluation was carried out before and 2 months after implantation. Anatomic evaluation was finally performed. Percutaneous pulmonary valve replacement was successful in 5 lambs. No complications were noted. Early and late angiographic and hemodynamic studies confirmed a good position of the stents with a competent valve at the end of the protocol. One stent was slightly stenotic, with macroscopically visible calcifications. CONCLUSIONS: Nonsurgical implantation of pulmonary valves is possible in the lamb. This new technique is similar to standard stent implantation. Thus, it should be feasible in humans, in whom it will lead to a significant reduction of reoperations in patients in need of pulmonary valve replacement.

Percutaneous balloon valvuloplasty in neonates with critical aortic stenosis.

Percutaneous balloon valvuloplasty was attempted in 10 newborn infants with critical aortic valve stenosis and severe congestive heart failure. Three had a very small left ventricle and aortic anulus. In one infant, the aortic valve could not be passed, and in another infant, a technical error resulted in severe valvular damage, aortic insufficiency and death. Among the eight patients who had effective dilation, the stenosis was relieved in seven as assessed by a significant decrease in transvalvular pressure gradient, improvement of left ventricular contraction and eventual inversion of the ductal shunting. The procedure failed in the only patient whose dilation was performed with an undersized balloon. Aortic insufficiency occurred in three infants and was severe (perforated cusp) in one, moderate in one whose valve was dilated with an excessively large balloon and mild and transient in one. None of the three infants with a very small left ventricle recovered (two died and one underwent cardiac transplantation). Among the seven infants with a left ventricle of acceptable size, three underwent subsequent aortic valvotomy; one of these died and two bad good results. The remaining four are doing well 16 +/- 5 months later (mean +/- SD) with mild to moderate residual aortic stenosis and normal left ventricular function. In conclusion, percutaneous balloon valvuloplasty is an acceptable alternative to surgery in neonates with critical aortic valve stenosis. Incidence of complications and good relief of the obstruction depend on a careful technique. Immediate results are similar to those of surgery. Late prognosis depends on the quality of the left heart structures.

A new strategy for the surgical treatment of aortic coarctation associated with ventricular septal defect in infants using an absorbable pulmonary artery band.

OBJECTIVES: We propose a new strategy using coarctation repair together with a polidioxanone absorbable pulmonary artery banding to limit operative risk and to spare infants with aortic coarctation subsequent operations. BACKGROUND: The alternative for the surgical management of aortic coarctation associated with ventricular septal defect (VSD) is single-stage repair versus coarctation repair with or without banding of the pulmonary artery. METHODS: Eleven infants (mean weight 2,560 +/- 1,750 g, range 1,320 to 3,800 g) underwent a coarctation repair with a polydioxanone banding. Seven had a trabecular and four a perimembranous VSD. The mean size of the VSD was 5 +/- 0.7 mm (range 4 to 7 mm). The systolic pulmonary pressure was >80% of the aortic pressure in all. The pulmonary band was tightened until the systolic pulmonary pressure fell below 50% of the aortic pressure. RESULTS: There were no hospital deaths. The reabsorption of the banding was complete after 5.7 months in all patients (3 to 6.5 months). The VSD closed completely in four infants and partially in six, in whom the pulmonary artery pressure was normal without evidence for significant left-to-right shunt. One patient with a large trabecular VSD underwent surgical closure of his defect after four months. Finally, a subsequent open-heart surgery could be avoided in 91% (10/11) of patients. CONCLUSIONS: Provided the VSD belongs to types prone to close spontaneously, this policy may reduce the number of surgical procedures per infant as well as in-hospital mortality and morbidity rates. It should be proposed as an alternative to more complex procedures.

Balloon valvotomy for critical stenosis or atresia of pulmonary valve in newborns.

OBJECTIVES: Percutaneous balloon valvotomy was studied retrospectively in newborns with critical pulmonary valve stenosis or atresia to assess its potential role as an alternative therapy to operation. BACKGROUND: Severe right ventricular outflow tract obstructions are life-threatening conditions requiring prostaglandin infusion immediately after birth and then relief of the valvular obstruction. To avoid surgical hazards at this age, it would be useful to extend to newborns the balloon valvotomy so effective in older patients. METHODS: Ninety-seven newborns (82 with critical pulmonary valve stenosis, 15 with atresia) underwent balloon valvotomy, provided that they had a well developed right ventricle, including an infundibulum close to the pulmonary artery. In patients with atresia, the outflow tract membrane had to be perforated with a wire needle or a radiofrequency probe. RESULTS: Balloon valvotomy could be performed in 81 patients and was effective in 77. It caused 3 fatal and 16 nonfatal complications. Ten patients with persistent poor right ventricular compliance despite an effective valvotomy required a surgical shunt. Among the 81 patients in whom the procedure could be performed, right ventricular surgery was avoided in 5 (55%) of the 9 patients with atresia (95% confidence interval [CI] 28% to 80%) and 55 (76%) of the 72 patients with stenosis (95% CI 66% to 86%) at the end of the follow-up period (9.7 years). CONCLUSIONS: Balloon pulmonary valvotomy is not always feasible in newborns, but it is relatively safe and effective and should be considered a valid alternative to operation.

Coronary artery obstruction after the arterial switch operation for transposition of the great arteries in newborns.

OBJECTIVES: We sought to describe a large series of coronary artery obstructions after the arterial switch operation for transposition of the great arteries and to discuss their clinical implications. BACKGROUND: Aortic root angiography and myocardial perfusion imaging yield ambiguous results regarding the fate of the coronary artery anastomoses after the arterial switch operation. Late death related to coronary artery obstruction and growth of the translocated coronary arteries are of major concern in these patients. METHODS: Selective coronary artery angiography was performed prospectively in a total of 165 children. RESULTS: A total of 12 coronary occlusions, 8 major stenoses, 6 minor stenoses of the left ostium and 4 stretchings of one coronary artery were identified. Obstructions were more frequent in types D and E (p < 0.001) of the Yacoub and Radley-Smith classification. Coronary obstruction was documented in all patients with electrocardiographic and ultrasound evidence of myocardial ischemia at time of study. Early postoperative ischemia did not predict coronary artery lesion if the patient had fully recovered. Persistent or delayed myocardial ischemia was highly predictive of coronary artery lesions. The incidence of coronary artery obstruction was very high (11 of 35) in patients operated on by a rapidly abandoned technique of single-orifice reimplantation of both coronary artery ostia. CONCLUSIONS: Selective coronary angiography is the most accurate means to assess coronary artery obstruction after the arterial switch operation. Precise diagnosis of coronary artery lesions after this operation will help to elucidate the pathogenesis, develop adequate therapeutic strategies and might indicate how to prevent coronary complications after operation.

Arterial mechanical changes in children with familial hypercholesterolemia.

Atherosclerosis is preceded by a phase of changes in the arterial wall that could have functional consequences even before the appearance of atheromatous changes. We hypothesized that early alterations of the mechanical properties of the arterial wall could precede clinical and echographic modifications. We used an automatic, computerized, ultrasonic procedure to evaluate geometric and mechanical characteristics of the common carotid artery (CCA) in normotensive children with primary familial class IIA hypercholesterolemia (FH; n=30; mean+/-SD age, 11+/-2 years old; mean+/-SD systolic/diastolic blood pressure, 109+/-9/55+/-7 mm Hg). These subjects were compared with age-matched, nonobese control subjects (n=27; 11+/-3 years old; 112+/-10/55+/-7 mm Hg). Noninvasive ultrasonic measurements were performed by the same investigator to measure the CCA luminal systolic and diastolic diameters and intima-media thickness (IMT). The cross-sectional compliance, cross-sectional distensibility, and the incremental elastic modulus of the CCA wall were then calculated. Finally, we assessed the degree of reactive hyperemia in the brachial artery produced after distal cuff occlusion and release. The changes in brachial arterial diameter in response to reactive hyperemia (endothelium-dependent dilation) and to glyceryltrinitrate (endothelium-independent dilation) were then measured. In patients with FH, we observed a significant reduction of systodiastolic variations in diameter (by 20%, P:<0.001) without a significant difference in IMT. Cross-sectional compliance and cross-sectional distensibility were significantly reduced in FH subjects (by 15%, P:<0.05 and 19%, P:<0.01, respectively). In parallel, the incremental elastic modulus was significantly increased (by 27%, P:<0.01) in children with FH. No correlation was evident between the carotid incremental modulus and either IMT or plasma low density lipoprotein cholesterol level. There was no difference in diameter of the brachial artery at rest in control and FH subjects (3.0+/-0.5 versus 3.0+/-0.4 mm). The reactive hyperemia and glyceryltrinitrate dilation were also similar in the 2 groups. However, the flow-mediated dilation of the brachial artery was smaller in the FH subjects (4.2+/-2.9%) than in controls (9.0+/-3.1%, P:<0.001). In FH, endothelium-dependent dilation was negatively correlated with the plasma low density lipoprotein cholesterol level (P:<0.04). These results indicate that increased stiffness of the CCA wall in children with FH is independent of blood pressure and could be related to endothelial dysfunction. Thus, alterations in CCA wall mechanics could be early and easily measurable markers of atheromatous changes in the arterial wall.

beta(1)-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a clinically recognisable contiguous gene syndrome ascribed to interstitial deletions of chromosome 17p11.2. Patients have a phase shift of their circadian rhythm of melatonin with a paradoxical diurnal secretion of the hormone. Serum melatonin levels and day-night behaviour were studied in nine SMS children (aged 4 to 17 years) given acebutolol, a selective beta(1)-adrenergic antagonist (10 mg/kg early in the morning). Cardiac examination, serum melatonin, motor activity recordings, and sleep diaries were monitored before and after drug administration. The present study shows that a single morning dose of acebutolol suppressed the inappropriate secretion of melatonin in SMS. A significant improvement of inappropriate behaviour with increased concentration, delayed sleep onset, increased hours of sleep, and delayed waking were also noted. These results suggest that beta(1)-adrenergic antagonists help to manage hyperactivity, enhance cognitive performance, and reduce sleep disorders in SMS.