RECURRENCE OF POMPE DISEASE IN FIRST COUSINS.

We report on the cases of two first-degree non-consanguineous cousins with infantile-onset Pompe disease, a rare autosomal recessive disease. The first patient developed cardiorespiratory failure at age 1 year. When she was 4 her male cousin developed hypotonia during his first month of life. Both infants had cardiac hypertrophy at diagnosis and shared the c.1927G>A missense mutation. Since a first degree cousin of an affected patient has 50 times the risk of developing the disease compared with unrelated infants and since cardiac hypertrophy is constant in affected infants, the combination of cardiac symptoms with a history of Pompe disease in a first degree cousin leads to a very high probability of having the condition. Clinically oriented screening based on simple diagnostic procedures such as echocardiogram and anamnesis could accelerate the initiation of enzyme replacement therapy of the deficient acid α-glucosidase which is critical to restoring cardiac function in affected infants.

Impact of COVID-19 disease on clinical research in pediatric and congenital cardiology.

BACKGROUND: COVID-19 triggered an unprecedented crisis affecting society at every level. Research in pediatric and congenital cardiology is currently in full development and may have been disrupted. The aim of the study was to determine the impact of COVID-19 on pediatric and congenital cardiology clinical research and to analyze decision-making and adaptation processes, from a panel of ongoing academic and industry-sponsored research at the time of the pandemic. METHODS: This observational study was carried out in April 2020, from a CHD clinical research network involving five tertiary care pediatric and congenital cardiology centers. Investigators and clinical research assistants from each participating research center completed an online survey questionnaire, and each principal investigator underwent a 1-h web-based videoconference interview. RESULTS: A total of 34 study questionnaires were collected, reporting that 18 studies were totally suspended. Upon the investigator's decision, after discussion on ethical issues and with facilitating support from health authorities, 16 studies were resumed. The rate of study suspension in interventional research (53%) was similar to that in non-interventional research (56%). Logistical problems were predominantly reported in both continued and suspended trials. Research protocols were adapted, largely thanks to telemedicine, which in some cases even improved the course of the study. CONCLUSION: The impact of the COVID-19 pandemic on clinical research in pediatric and congenital cardiology has been limited by a rapid adaptation of all research structures and an extensive use of telemedicine at all stages of the studies.

[Use of levosimendan in children]. / Utilisation du levosimendan chez l'enfant.

Levosimendan is a calcium-sensitizing drug with positive inotropic properties. As an inodilator, this molecule also has a vasodilation effect. While its efficacy has been demonstrated in the adult in the context of cardiac surgery, its pediatric use is still not widespread. Many studies have shown its safety of use in children, including in the newborn. Across the world, a growing number of teams use levosimendan to treat both acute and chronic heart failure. Through a review of the literature, we describe its pharmacodynamic effects, its current applications, and its perspectives of use in children.

Evaluation of nutritional status and support in children with congenital heart disease.

BACKGROUND/OBJECTIVES: The objective of this disease was to determine the prevalence of malnutrition in children with congenital heart disease (CHD). SUBJECTS/METHODS: A total of 125 children with CHD, under 6 months of age, were divided into four groups: no pulmonary hypertension (PH) or cyanosis (group 1, n=47), isolated cyanosis (group 2, n=52), isolated PH (group 3, n=16), and PH and cyanosis (group 4, n=10). Six children died at 6 months (n=4), 12 months (n=1) and 19 months (n=1). The remaining children were followed-up for 24 months. Prevalence of moderate to severe malnutrition (weight/weight for height <80%), caloric intake and medications were compared between the four groups. RESULTS: Moderate or severe malnutrition was more frequent in group 4 (100%) compared with others groups (group 1, 20%; group 2, 16.7% and group 3, 50%; P<0.05). Low oral caloric intake was more frequent in group 3 (71.4%) and group 4 (75%) than in group 1 (28%) and 2 (28.6%) (P<0.05). Food enrichment was practised in half of the children of group 4 and rarely in other groups (group 1, 15.8%; group 2, 8.6% and group 3, 11.1%; P<0.05). Enteral feeding was used more often in groups 3 (33.3%) and 4 (50%) than in groups 1 (15.8%) or 2 (14.3%; P<0.05). CONCLUSIONS: Moderate or severe malnutrition is present in 15% of children with CHD, and it is more frequent in case of PH. Half of these children demonstrate low caloric intake, whereas few have proper nutritional support.

[Arterial rigidity of patients operated successfully for coarctation of the aorta without residual hypertension]. / Etude de la rigidité artérielle des patients opérés avec succès d'une coarctation de l'aorte sans hypertension résiduelle.

In patients successfully operated for coarctation of the aorta, the prevalence of hypertension is higher than that observed in the general population although the exact mechanism is not known. The hypothesis of increased arterial rigidity despite satisfactory correction of the coarctation has been proposed. The authors undertook 24 hour ambulatory blood pressure monitoring coupled with measurement of the QKD interval (pulse wave velocity) in order to evaluate the rigidity of the large arteries. These results were compared with those obtained in control patients paired with respect to gender, age, height and weight. Twenty-six patients with an average age of 14.5 +/- 2.9 years were included (age at time of surgery 6.3 +/- 3.7 years). The statistical data confirmed a higher systolic blood pressure (p<0.05) in the operated patients compared with controls. The results confirm the hypothesis of increased residual arterial rigidity in children operated for coarctation of the aorta which could predispose to secondary hypertension, especially on effort. In the long term, this could be an unquestionable cardiovascular risk factor explaining the increased cardiovascular morbid-mortality compared with the general population.

[Outcome of 30 congenital atrio-ventricular blocks]. / Devenir à long terme de 30 blocs auriculo-ventriculaires complets congénitaux isolés.

Congenital isolated atrio-ventricular block (CAVB) is a rare pathology, and its management is still rather poorly described through international literature. Within the service of pediatric cardiology leaded by Pr Choussat and Dr Jimenez (Cardiologic Hospital Haut-Lévêque of Bordeaux), we collected from 1980 to 2003, 30 isolated congenital CAVB, constituting the purpose of this retrospective study. Average follow-up is 14 +/- 8.8 years. None death occurred. CAVB are discovered at an average age of 4.8 years old; 6 cases were diagnosed in utero, half of them were associated with maternal lupus. Twenty patients on 30 were fitted with stimulator at an average age of 8.7 +/- 6.9 years old, due to symptoms or bradycardy. Epicardic fitting in VVI mode represents 65% of first approaches, it is followed by endocavitary way for 81% of cases. Cardiac stimulation does not prevent from dilated cardiomyopathy. Among 30 patients 10 were not fitted with stimulator, half of them presents chronotrop insufficiency during effort. As a conclusion, our patients show a good long-term vital prognosis; although CAVB discovered in utero lead to worse prognosis for children.

[Asynchronism and right ventricular pacing]. / Asynchronisme et stimulation ventriculaire droite. Démonstration de l'effet délétère d'une stimulation apicale dans une population d'adultes appareillés pour BAV congénital.

UNLABELLED: In patients with congenital heart block (CHB), dual-chamber pacing restores physiological heart rate and atrio-ventricular synchronization. However, patients with narrow QRS junctional escape rhythm may be deleteriously affected by long-term, permanent, apical ventricular pacing. We assessed the impact of apical ventricular pacing on echocardiographic ventricular dyssynchrony and hemodynamic parameters. METHODS: Fourteen CHB adults (23 +/- years, 58% male), with a DDD transvenous pacemaker and a junctional escape rhythm (QRS<120 ms) before implantation, were studied. Echocardiography coupled with tissue Doppler imaging (TDI) and Strain rate was performed in spontaneous rhythm (VVI mode 30/mn) and during atrio-synchronized ventricular pacing. RESULTS: The heart rate (43 +/- 09 vs 68 +/- 07: p<0.01), cardiac output (2.9 +/- 0.7 vs 3.7 +/- 0.6 L/min) and left ventricular filling time (325 +/- 38 vs 412 +/- 51 ms; p<0.01) were significantly less in the escape spontaneous rhythm compared with atrio-ventricular synchronized apical pacing. However, interventricular dyssynchrony (28 +/- 12 vs 59 +/- 25 ms, p<0.05), intra-left ventricular dyssynchrony (36 +/- 11 vs 57 +/- 29 ms; p<0.05), extent of left ventricular myocardium displaying delayed longitudinal contraction (26 +/- 10 vs 39 +/- 17%: p<0.05) were significantly less in the escape rhythm compared with paced rhythm. CONCLUSION: Once implanted with a DDD pacemaker, CHB patients present with increased cardiac output secondary to the restoration of physiological heart rate and improved diastolic function. However, the apical site is not optimal, as it creates detrimental ventricular dyssynchrony in patients with previous nearly physiological ventricular activation. Alternative pacing sites should be investigated.

Ductal closure and near-infrared spectroscopy for regional oxygenation monitoring in ductus-dependent congenital heart disease.

In ductus-dependent congenital heart disease, preserving the blood flow through the ductus arteriosus (DA) is vital before surgery. We present the cases of three full-term neonates with ductus-dependent congenital heart disease for whom near-infrared spectroscopy (NIRS) monitoring was performed. We recorded cyclical drops in regional oxygen saturation, both cerebral and renal, that corresponded to constrictions of the DA. These findings appeared either simultaneously or previous to SpO2 drops and were corrected by prostaglandin infusion. Through these cases, we assume that cyclical constrictions of ductal cells participate in the DA closure process in its early phase.

[Factors predictive of mortality in Ebstein's anomaly]. / Facteurs prédictifs de mortalité dans la maladie d'Ebstein.

Nearly 150 years after the description of Ebstein's anomaly the prognostic factors are not well known. Besides the foetal and neonatal forms which carry a poor prognosis the adult forms are often well tolerated and pose the difficult problem of management. This was a retrospective study of 73 patients with this malformation followed up between 1967 and 2002 at the University Hospital of Bordeaux. There were 14 deaths (19%) half of which (7) occurred during the first 3 months of life. The factors predictive of mortality (p<0.05) were: age, associated malformations, Classes III-IV of the New York Heart Association, cardiac failure, malaises, cyanosis, a raised cardiothoracic index, and a high mitro-tricuspid displacement indexed to body surface area. Supraventricular arrhythmia and the Wolff-Parkinson-White syndome do not seem to be associated with extramortality. Surgery, with reference to published studies, seems to improve survival, functional status and decrease the prevalence of arrhythmias. It would appear to be justified to propose surgery when functional status declines or when signs of poor prognosis are observed.

[Outcome of operated Fallot's tetralogy]. / Devenir des tétralogies de Fallot opérées.

Fifty years after the beginning of cardiac surgery, a large percentage of operated congenital heart disease patients attain adulthood. The tetralogy of Fallot is one of the malformations in which the natural outcome was unfortunately nearly fatal in the long-term. Open heart surgery has radically transformed the prognosis of this, the most common of all cyanotic congenital cardiac malformations. Nowadays, most operated patients lead normal professional and family lives. Lonf-term survival after correction is between 90-95% after 30-35 years. Although surgical repair is satisfactory, the operated heart is not anatomically normal. The patients have a variable degree of devalvulation of the pulmonary outflow tract, a scar on the right ventricle, a patch repairing the ventricular septal defect and scars on the atrium (cannulation for cardiopulmonary bypass). These sequellae expose the patients to a number of complications, notably arrhythmic and sometimes haemodynamic, affecting the right ventricle. The late mortality rate varies from 5 to 13% in the literature. The main causes of death are sudden death and reoperation. Sudden death is the most severe long-term complication but it is uncommon, affecting less than 5% of the population. It is mainly due to ventricular arrhythmias. Certain predisposing factors should be identified during long-term follow-up, among them the presence of haemodynamic abnormalities: systolic overload (residual pulmonary stenosis) or diastolic overload of the right ventricle (pulmonary regurgitation), infundibular aneurysm, right ventricular dysfunction. It would appear to be important to prevent pulmonary regurgitation by preserving the pulmonary valve even if it means persistence of a mild transvalvular pressure gradient. When pulmonary regurgitation is inevitable, follow-up is essential to evaluate the timing of valvulation of the pulmonary orifice. Despite these different complications which must be understood for proper follow-up of these patients, the long-term outcome of operated tetralogy of Fallot remains very good.

[Ectopic junctional tachycardia of the neonate]. / Tachycardie jonctionnelle ectopique du nouveau-né. A propos de 2 cas.

Congenital ectopic junctional tachycardia (EJT) is a rare arrhythmia presenting in the first 6 months of life. It is often resistant to antiarrhythmic drugs and its poor prognosis (35% mortality) explains its often complex management. The authors report two cases which illustrate its unpredictability with a potential to degenerate to serious ventricular arrhythmias. The possibility of progression to atrioventricular block, increased by antiarrhythmic therapy, may lead to implantation of a cardiac pacemaker. The poor outcome of the two babies underlines the severity of these arrhythmias.

[Ebstein's anomaly]. / Anomalie d'Ebstein.

Since Ebstein's first description in 1866 and the first surgical attempts at treatment in the 1950's, the natural history of this condition remains obscure. The anatomical description contrasts with the clinical and prognostic variability of this malformation. The form observed in the foetal or prenatal periods has a very different prognosis to that observed in adults. The risk factors are not the same even though the anatomical entity is comparable. The difficulty in managing these patients is due to the problems of diagnosis and determination of these prognostic factors. Advances in echocardiography, the key investigation which facilitates diagnosis, and in surgical and ablation techniques, have improved our understanding of this condition and its prognosis.

[Diagnostic and therapeutic value of lymphography in persistent postoperative chylothorax]. / Intérêt diagnostique et thérapeutique de la lymphographie dans un chylothorax postopératoire persistant.

Chylothorax is a rare but generally severe complication of surgery of congenital heart disease. The authors report the clinical history of a young boy with complex congenital heart disease operated on several occasions and who developed severe and recurrent unilateral chylothorac after a bicavo-bipulmonary derivation. Conservative treatment followed by continuous somatostatin infusion was ineffective. Diagnostic Lipiodol lymphography was required before the chylothorax was cured. The authors describe management of this difficult case and discuss the therapeutic possibilities with reference to a brief review of the literature.

[Placement of an implantable defibrillator via the endocavitary route in a patient presenting with a univentricular heart and a Glenn anastomosis]. / Pose d'un défibrillateur implantable par voie endocavitaire chez une patiente présentant un coeur univentriculaire et une anastomose de Glenn.

We report the observation of a female 45 year old patient presenting with a post-surgery complex congenital cardiopathy, associated with serious ventricular rhythm disorders necessitating the placement of an implantable defibrillator. The palliative surgery performed (cavo-pulmonary Glenn anastomosis) does not allow the usual access to the right ventricle via the superior vena cava. The different possibilities for defibrillator implantation are discussed. These include associating a surgical approach to introduce the bipolar probe with subcutaneous tunnelling to connect the probe to the box.

Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase.

M. N. Laclau, S. Boudina, J. B. Thambo, L. Tariosse, G. Gouverneur, S. Bonoron-Adèle, V. A. Saks, K. D. Garlid and P. Dos Santos. Cardioprotection by Ischemic Preconditioning Preserves Mitochondrial Function and Functional Coupling Between Adenine Nucleotide Translocase and Creatine Kinase. Journal of Molecular and Cellular Cardiology (2001) 33, 947-956. This study investigates the effect of ischemic preconditioning on mitochondrial function, including functional coupling between the adenine nucleotide translocase and mitochondrial creatine kinase, which is among the first reactions to be altered in ischemia. Three groups of Langendorff-perfused rat hearts were studied: a control group, a group subjected to 30 min ischemia followed by 15 min reperfusion, and a group subjected to ischemic preconditioning prior to 30 min ischemia and 15 min reperfusion. Ischemic preconditioning significantly delayed the onset and amplitude of contracture during ischemia, decreased enzymatic release, and improved the recovery of heart contractile function after reperfusion. Mitochondrial function was assessed in permeabilized skinned fibers. The protective effect of preconditioning was associated with preservation of mitochondrial function, as evidenced by maintenance of the high K(1/2)for ADP in regulation of mitochondrial respiration and V(max)of respiration, the near absence of respiratory stimulation by exogenous cytochrome c, and preservation of functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase. These data suggest that ischemic preconditioning preserves the structure-function of the intermembrane space, perhaps by opening the mitochondrial ATP-sensitive K(+)channel. The consequence is preservation of energy transfer processes from mitochondria to ATP-utilizing sites in the cytosol. Both of these factors may contribute to cardioprotection and better functional recovery of preconditioned hearts.