Transposition of the great arteries: factors influencing prenatal diagnosis.

OBJECTIVE: The objective of this study is to highlight the factors that may affect prenatal diagnosis of transposition of the great arteries (TGA) in order to improve it. METHODS: This is a retrospective study performed between 2004 and 2009 in the maternity units from North of France. We identified a total of 68 cases of TGA (isolated or associated with only VSD or coarctation of aorta), of which 32 (47.1%) had prenatal diagnosis (PND+) and 36 did not (PND-). Maternal characteristics and ultrasound factors were studied in relation to PND. RESULTS: Maternal weight and body mass index were significantly higher in the PND- group (70.4 kg and 26.5 kg/m(2) vs 63.6 kg and 23.6 kg/m(2) , respectively). Maternal obesity (body mass index >30) was significantly more frequent in the PND- group (27.8% vs 12.5%). More than a quarter of TGA (28.1%) were diagnosed during the third trimester. CONCLUSION: Obesity is the main cause of missed PND of TGA. Obese patients with suboptimal prenatal scans may benefit from reassessment of fetal cardiac anatomy and/or from referral for fetal echocardiography.

[Syncope and pre-syncope in children and adolescents: a prospective study in a pediatric emergency care unit]. / Syncopes et lipothymies chez l'enfant et l'adolescent : étude prospective dans une unité d'urgence pédiatrique.

OBJECTIVES: To assess in a pediatric emergency care unit (PECU): 1. The frequency of syncope and pre-syncope, 2. The incidence of diagnoses, 3. The value of investigations and cardiology and neurology consultations. METHODS: The data of PECU patients aged 2 years to 15 years and 3 months were prospectively collected over 1 year. Standard electrocardiogram and serum glucose were compulsory investigations. Schellong's orthostatic test was performed whenever possible. RESULTS: One hundred and fity-nine children (mean age, 11+/-4 years) were included, accounting for 0.8% of the PECU's visits: 48% had syncope, 52% had pre-syncope. The most common cause was neurally mediated syncope - 98 patients (62%), with vasovagal syncope for 80 patients - followed by neurological causes: 29 patients (18%). Neither cardiac arrhythmia nor obstructive cardiomyopathy was diagnosed. There were discrepancies between cardiologists' and pediatricians' ECG interpretations in 9% of cases. Diagnoses differed between cardiologists and pediatricians in 54% of 41 consultations. Diagnoses differed between neurologists and pediatricians in 54% of 42 consultations. No investigation except Schellong's orthostatic test led to modification of a previous diagnosis. CONCLUSION: This study emphasizes that the routine workup of pediatric syncope should focus on the patient's history and physical examination. Diagnostic testing should be minimal: ECG and Schellong's orthostatic test. The leading cause was neurocardiogenic syncope.

[The Jervell and Lange-Nielsen syndrome. Natural history, molecular basis and clinical outcome]. / Syndrome de Jervell et Lange-Nielsen. Histoire naturelle, bases moléculaires et devenir clinique.

UNLABELLED: Data on the Jervell and Lange-Nielsen syndrome (JLN), the long QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the IKs current, are still largely based on case reports. We analyzed data from 186 JLN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events and 50% were symptomatic already by age 3. Their QTc was markedly prolonged (557 +/- 65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD). A QTc>550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. beta-blockers have only partial efficacy as 51% of the patients had events despite therapy and 29% had CA/SD. CONCLUSIONS: JLN syndrome is a most severe variant of LQTS, with a very early onset, major QTc prolongation, and is not well responsive to beta-blockers. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc pound550 ms, without events in the first year of life, and with mutations on KCNE1. Early therapy with ICDs has to be considered.

Permanent junctional reciprocating tachycardia in children: a multicentre study on clinical profile and outcome.

OBJECTIVES: To investigate the clinical profile, natural history, and optimal management of persistent or permanent junctional reciprocating tachycardia (PJRT) in children. METHODS AND RESULTS: 85 patients meeting the ECG criteria for PJRT were enrolled in a retrospective multicentre study. Age at diagnosis varied from birth to 20 years (median 3 months). Follow up ranged from 0.1 to 26.0 (median 8.2) years. At the time of referral, 24 of 85 patients (28%) had congestive heart failure that was resolved with medical treatment in all patients. Eighty three patients received drug treatment initially. Amiodarone and verapamil were the most effective with a success rate of 84-94% alone or in association with digoxin. Radiofrequency ablation of the accessory pathway was performed in 18 patients. There was a trend for a relation between age at ablation and the result of the procedure, failures being more common in younger patients (three of six procedures in younger and 15 of 18 in older children were successful; p = 0.14). Two patients with persistent left ventricular dysfunction on echocardiography but with no symptoms of congestive heart failure died suddenly one month and three years after diagnosis. PJRT resolved spontaneously in 19 patients (22%). Age at diagnosis of PJRT was not a predictor of spontaneous resolution. CONCLUSIONS: PJRT is a potentially lethal arrhythmia in children with tachycardia induced cardiomyopathy. Spontaneous resolution of tachycardia is not uncommon. Antiarrhythmic treatment is often effective. Radiofrequency ablation should be performed in older children or when rate is not controlled, especially in patients with persistent left ventricular dysfunction.

Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients.

BACKGROUND: The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands. METHODS AND RESULTS: We identified 13 missense mutations in the cardiac ryanodine receptor (RYR2) in 12 probands with CPVT. Twelve were new, of which two are de novo mutations. A further 11 patients were silent gene carriers, suggesting that some mutations are associated with low penetrance. A marked resting sinus bradycardia off drugs was observed in all carriers. On beta blocker treatment, 98% of the RYR2 mutation carriers remained symptom free with a median follow up of 2 (range: 2-37) years. CONCLUSION: CPVT patients with RYR2 mutation have bradycardia regardless of the site of the mutation, which could direct molecular diagnosis in (young) patients without structural heart disease presenting with syncopal events and a slow heart rate but with normal QTc at resting ECG. Treatment with beta blockers has been very effective in our CPVT patients during initial or short term follow up. Given the risk of sudden death and the efficacy of beta blocker therapy, the identification of large numbers of RYR2 mutations thus calls for genetic screening, early diagnosis, and subsequent preventive strategies.

Severity of the ductal shunt: a comparison of different markers.

BACKGROUND: When the ductus arteriosus (DA) is patent, the ductal shunt is proportional to the ratio of left ventricular output (LVO) to systemic blood flow. Systemic blood flow can be estimated by measuring flow in the superior vena cava (SVC). OBJECTIVE: To re-evaluate the accuracy of standard echocardiographic markers of patent ductus arteriosus (PDA) using LVO/SVC flow ratio. METHODS: Prospective study. Preterm infants of 24-30 weeks gestational age and postnatal age less than 48 hours. The following echocardiographic criteria were measured: left atrial to aortic root ratio (LA/Ao); DA diameter by B mode and colour Doppler; mean and end diastolic flow velocity of the left pulmonary artery (LPA); LVO; SVC flow. RESULTS: Twenty three preterm infants were enrolled (median gestational age 28 weeks (range 24-30), median birth weight 840 g (500-1440)). The DA was closed in eight (mean (SD) LVO/SVC 2.4 (0.3)) and open in 15 (mean (SD) LVO/SVC 4.5 (0.6)). An LA/Ao ratio > or =1.4, a DA diameter > or =1.4 mm/kg, and a mean and end diastolic flow velocity of LPA respectively > or =0.42 and > or =0.20 m/s identified an LVO/SVC > or =4 with a sensitivity and a specificity above 90%. CONCLUSION: This study indicates that LA/Ao ratio, DA diameter, and mean and end diastolic flow velocity of the LPA are accurate markers of PDA. These standard echocardiographic variables are easy to measure and need less skill and resources than direct measurements of ductal shunt.

Assessing sleeping energy expenditure in children using heart-rate monitoring calibrated against open-circuit indirect calorimetry: a pilot study.

Total energy expenditure (EE) can be assessed in children by the heart-rate (HR) monitoring technique calibrated against open-circuit indirect calorimetry (IC). In this technique, sleeping EE is usually estimated as the lowest value of a 30 min resting EE measurement x 0 x 90 to give an average for the total sleeping period. However, sleeping is a dynamic process in which sleeping EE is modulated by the effect of factors such as body movement and different sleep stages. The aim of the present study was to determine a new method to improve the sleeping EE measurement by taking into account body movements during sleep. Twenty-four non-obese children participated in the present study. All subjects passed through a calibration period. HR and EE measured by IC were simultaneously collected during resting, the postprandial period, and during different levels of activity. Different methods for computing sleeping EE (resting with different breakpoints ('flex point' HR with linear regression or 'inflection point' (IP) HR with the third order polynomial regression equation (P3)) were compared with EE measured for least 2.0 h in eight sleeping children. The best method of calculation was then tested in sixteen children undergoing HR monitoring and with a body movement detector. In a subset of eight children undergoing simultaneous sleeping EE measurement by IC and HR, the use of the equation resting when HRIP during the sleeping period gave the lowest difference (1 (sd 5.4) %) compared with other methods (linear or polynomial regressions). The new formula was tested in an independent subset of sixteen other children. The difference between sleeping EE computed with the formula resting and sleeping EE computed with resting when HRIP during sleeping periods was significant (13 (sd 5.9) %) only for active sleeping subjects (n 6 of 16 subjects). The correlation between the difference in the results from the two methods of calculation and body movements was close (r 0.63, P<0.005, Spearman test) as well as computed sleeping EE (Spearman test, r 0.679, P<0.001), indicating that this new method is reliable for computing sleeping EE with HR monitoring if children are moving during sleep and improves the total EE assessment.

[Purpura fulminans and coxsackie B2 co-infection]. / Purpura fulminans et co-infection à coxsackie B2.

INTRODUCTION: During septic shock in children, myocardial deficiency usually lasts 3 to 6 days. When prolonged, an other etiology should be looked for. OBSERVATION: A 29 month-old child presented with purpura fulminans, probably due to Neisseria meningitidis. Positivity of the serodiagnostic for coxsackie B2, performed because of persisting myocardial deficiency, evoked diagnosis of a coxsackie B2 co-infection. DISCUSSION: Abnormally prolonged myocardial deficiency during purpura fulminans must lead to the search for a congenital, metabolic or infectious cardiomyopathy.

Long-term follow-up of children and adolescents with syncope; predictor of syncope recurrence.

BACKGROUND: Previous studies have shown that investigation by tilt testing is very appropriate in paediatrics, but the characteristics of children and adolescents who are at high risk of recurrent syncope, once the diagnosis is established, remain unclear. This study was set up to analyse the risk factors attributed to syncope recurrence in paediatric patients. METHODS: One hundred and one children and adolescents aged 7 to 18 years, undergoing a tilt test for recurrent syncope, were studied. They were subsequently followed-up in clinic visits with a final interview at the clinic or by telephone at the end of the follow-up period. RESULTS: A head-up tilt test elicited syncope or pre-syncope in 67 children. The positive responses included vasovagal syncope in 58 patients and psychogenic syncope in nine patients. Gender, age, number of pre-tilt test syncopal episodes or duration of symptoms made no difference to children with positive or negative tilt test results. Following the tilt test, 43 of 67 children with a positive tilt test were treated empirically. No treatment was prescribed for the remaining 24 with a positive test, or for those with a negative tilt test. There were no differences between treated and untreated children with respect to the number of pre-tilt test syncopes, duration of symptoms and duration of follow-up. Follow-up data were available in 97 children. During a mean follow-up of 46+/-28 months, syncope recurred in 31 children (32%). The recurrence rate was similar between positive and negative tilt test groups (22/66 vs 9/31, respectively; P=ns), as well as between treated and untreated children (14/43 vs 8/23, respectively; P=ns). When comparing syncope-free children at follow-up in a univariate analysis, children with recurrent syncope reported a greater number of historical syncopal spells (7+/-8 vs 3+/-3, P=0.01). In addition linear correlation (r=0.6, 95% CI 0.47 to 0.72, P<0.0001) was significant between the number of historical syncope episodes and the risk of recurrent syncope. CONCLUSIONS: These findings suggest that the risk of syncope recurrence for children and adolescents with such a history is not correlated to the tilt test result or prophylactic treatment. The number of historical syncopal spells is, however, predictive.

[Percutaneous closure of patent ductus arteriosus with the Amplatzer duct occluder. Results of 29 patients]. / Fermeture percutanée du canal artériel avec le dispositif Amplatzer duct occluder. Série de 29 patients.

The authors report their experience of percutaneous closure of large patent ductus arteriosus with the Amplatzer duct occluder. The age of the patients ranged from 3 months to 72 years (average 24 months) with body weights of 3.9 to 74 Kg (average 16 Kg). The smallest angiographic diameter of the ductus was 4.0 +/- 1.3 mm at angiography (range 1.8 to 6 mm). The occluder was inserted under local anaesthetic with control aortography in all but one case who required general anaesthesia. In two small babies, the implantation was performed after venous puncture alone with transthoracic echocardiographic monitoring. The implantation was successful in all but one case in which there was a distensible duct. Early angiographic control showed suppression of the shunt in 61% of patients. Secondary haemolysis was observed in one case and was corrected by a second catheterisation 4 days later, with occlusion of the duct with a balloon catheter. The patients were followed up clinically, radiologically and echocardiographically. Doppler echocardiography showed absence of a residual shunt in 24 patients (86%) one month after the procedure, in 25 patients (89%) 3 months after the procedure and in 26 patients (93%) one year after the procedure. Two patients were left with mild or moderate shunts 12 and 16 months after the attempted occlusion. No cases of aortic or pulmonary obstruction were observed. The authors conclude that the Amplatzer duct occluder is a reliable device for closing large patent ductus arteriosus. It may be proposed in young symptomatic children over 4 Kg in body weight. A high rate of occlusion is obtained with a minimal risk of complications.

[T wave abnormalities on Holter monitoring of congenital long QT syndrome: phenotypic marker of a mutation of LQT2 (HERG)]. / Anomalies de l'onde T au Holter dans le syndrome du QT long congénital: marqueur phénotypique d'une mutation dans LQT2 (HERG).

The two genes which code for the potassium channels, KCNQ1 and HERG, are responsible for the most common forms of the long QT syndrome, LQT1 and LQT2. Abnormalities of duration and morphology of the ventricular repolarisation are amongst the diagnostic criteria of this syndrome. The morphology of the T waves was studied by 24 hour Holter monitoring in 190 subjects with a long QT syndrome due to KCNQ1 (LQT1) [N = 133] or HERG (N = 57) and in 100 controls, and it was compared with the ECG T wave. The T wave was characterised according to 3 morphological features: grade 0 (G0) = normal, grade 1 (G&) = slight ST depression and grade 2 (G2) = presence of ST elevation of the descending phase of the T wave. The T wave morphology on Holter ECG was normal for most LQT1 and control subjects compared with LQT2 (92%, 96% and 19% respectively, p < 0.01). Grade 1 appearances were observed more often in LQT2 (18 vs 8% for LQT1 and 4% for controls, p < 0.01). Grade 2 appearances were only observed in the cases of LQT2 (63%). The predictive factors of G2 were young age and an anti-sense mutation of the transmembrane domaines of HERG. The authors conclude that Holter monitoring improves detection of T wave changes compared with the ECG. Grade 2 changes seem to be a phenotype marker for a HERG mutation, especially those situated in the transmembrane domaines.

[Left monoplegia revealing pulmonary arteriovenous fistual in an adolescent: occclusion with an Amplatzer occluder]. / Monoplégie gauche révélatrice d'une fistule artérioveineuse pulmonaire chez un adolescent: occlusion avec un bouchon d'Amplatz.

A 16 year old adolescent was admitted to hospital for investigation of a transient left monoplegia. The clinical, electric and radiological examinations were all normal. Echocardiography showed no abnormality of cardiac structures or function. Contrast echocardiography was performed and showed a right-to-left shunt suggesting a pulmonary arteriovenous fistula which was confirmed at angiography. The fistula was closed at catheterisation by a detachable balloon: in a second procedure, the balloon was deflated and contrast studies showed a recurrence of the right-to-left shunt. An Amplatzer 8/6 duct occluder was implanted with excellent results and no recurrence at 3 months.

[Value of an implantable EKG monitor for the diagnosis of arrhythmic syncope in children]. / Intérêt d'un moniteur ECG implantable pour le diagnostic de syncopes rythmiques chez l'enfant.

The value of an implantable ECG monitor (Reveal TM Plus) is reported in a 12 year old child with unexplained syncopal episodes despite extensive investigations. Twenty-seven days after the implantation, ventricular tachycardia at 450/min was recorded at the first recurrence. This case shows that this type of monitoring can be particularly useful when an arrhythmia is thought to be the cause of syncope in a child and the initial investigation is negative.

Notched T waves on Holter recordings enhance detection of patients with LQt2 (HERG) mutations.

BACKGROUND: The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T waves have been proposed as a phenotypic marker of LQTS patients. METHODS AND RESULTS: The T-wave morphology of carriers of mutations in KCNQ1 (n=133) or HERG (n=57) and of 100 control subjects was analyzed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P:<0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4% [control], P:<0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG. CONCLUSIONS: This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations.

Effects of transdermal nitroglycerin in children with congestive heart failure: a Doppler echocardiographic study.

The aim of this study was to evaluate by Doppler echocardiography whether administration of transdermal nitroglycerin (NTG) to children with congestive heart failure could modify mitral flow velocity profile with redistribution of left ventricular filling to late diastole, suggesting preload reduction of the left ventricle. Twelve children with congestive heart failure, aged from 6 months to 6 years (2.83 +/- 2.24 years; mean +/- SD), were recruited. Patients were randomly allocated either a NTG patch (study group; n = 6) or a placebo patch (control group; n = 6) in a double-blind procedure. The NTG patch was a 10-cm(2) patch releasing 5 mg of NTG per day. NTG patches were adjusted to a dose of 1 cm(2)/kg/day (0.5 mg/kg/day). Peak velocity and time--velocity integral (TVI) of E and A waves of transmitral flow, the ratio of the velocities of the A wave and E wave, and the ratio of the TVI of the A wave to the TVI of the E wave were measured. Doppler measurements were determined before treatment (H0) and 4 hours (H4) and 23 hours (H23) after the patch application. Relative changes of these parameters were not significantly different between these two groups. In the NTG group, mean NTG plasma concentration was 1.08 +/- 0.47 microg Liter(-1) at H4 (n = 5) and 1.18 +/- 0.81 microg Liter(-1) at H23 (n = 5). No patient had a NTG plasma concentration greater than 2 microg Liter(-1) either at H3 or at H24. These data suggest that 1 cm(2)/kg transdermal doses of NTG may have a limited bioavailability or a higher clearance and minimal hemodynamic effects in children with congestive heart failure already receiving other medications, implying that higher doses should be used.

Signal-averaged electrocardiography in children with anthracycline-induced cardiomyopathy.

The aim of the present study was to determine if signal-averaged ECG of patients with anthracycline-induced left ventricular dysfunction could differentiate between patients with anthracycline-induced cardiotoxicity and those without. Sixteen children with anthracycline-induced cardiomyopathy, aged 6.5 to 15.5 years (anthracycline dose = 198-737 mg/m2), and 31 patients aged 5.0 to 16.7 years, who received anthracyclines without evidence of left ventricular dysfunction (anthracycline dose = 120-517 mg/m2), were studied with signal averaged ECG. The two groups were comparable in age, body surface area, and time since completion of chemotherapy. Signal averaged ECG parameters of the patients were compared with data obtained from 530 healthy children. These parameters were converted to z-scores to account for growth-related changes in signal averaged ECG recordings. Z-scores for filtered QRS duration and low amplitude terminal signal < 40 microV were significantly lower (p = 0.002 and p = 0.015, respectively), and Z-score for root mean square voltage of the last -30 ms of filtered QRS tended to be higher (p = 0.06) in patients with left ventricular dysfunction. Filtered QRS duration lower than -1.5 SD was found in 4 of 16 patients with left ventricular dysfunction and in only 1 of 31 patients without (p < 0.05) yielding a sensitivity of 25% and a specificity of 97% to detect left ventricular dysfunction. Only 1 patient had late potentials; his left ventricular function was normal. Left ventricular mass index tended to be lower in patients with left ventricular dysfunction (p = 0.07), whereas left ventricular diastolic diameter was similar in the two groups. The mechanism that accounted for the difference in signal averaged-ECG between the two groups of patients could be linked with the decrease in left ventricular mass in patients with left ventricular dysfunction. In conclusion, children with left ventricular dysfunction following anthracycline therapy have a SA ECG different from those without left ventricular dysfunction, which is mainly characterized by a lower filtered QRS duration. A prospective study is needed in order to determine if this modification of SA ECG recordings precedes alteration of left ventricular function, and, therefore, if it could help in early detection of cardiac toxicity of anthracyclines.

Experience in one centre using the buttoned device for occlusion of atrial septal defect: comparison with the Amplatzer septal occluder.

We report our experience using the buttoned device to close defects within the oval fossa and probe-patent oval foramens, comparing the findings with those obtained with the Amplatzer septal occluder. From 1992 to 1997, we used the buttoned device to close defects in 73 consecutive patients, 64 with defects in the oval fossa and nine with patent foramens. We compared this experience with a further series of 62 patients seen from 1997 to 1999 in whom the Amplatzer septal occluder was used. Successful implantation was achieved in three-quarters of those with septal defects in whom the buttoned device was used, in all of those in whom the buttoned device was used for patent foramens, and in nine-tenths of those in whom closure was attempted using the Amplatzer occluder. Immediate surgery was needed in 3 patients in whom a buttoned device was used, one because of embolization and two with residual shunts and a straddling device. Similar immediate surgery was needed to retrieve one embolized Amplatzer occluder. During follow-up, surgery was needed in a further 7 patients, all having had insertion of a buttoned device, because of atrial perforation in one and a significant residual shunt in the remainder. At late follow-up, the rate of complete occlusion was 69% in the patients in whom the buttoned device was used to close a septal defect, 100% when the buttoned device was used for patent foramens, and 95% in those treated with the Amplatzer occluder. Our experience shows that the Amplatzer occluder produced a significantly higher rate of occlusion for larger defects, and with a shorter fluoroscopy time than the buttoned device. The Amplatzer septal occluder, therefore, is our preferred device for closure of defects within the oval fossa.