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Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ministère de la Santé Française Background Arrhythmic risk stratification remains a major challenge in asymptomatic Brugada patients. Many studies have evaluated risk stratification performance based on a single or a few ECG-derived parameters measured manually. We aimed to assess the predictive value of multi ECG parameters measured automatically in patients with Brugada syndrome. Materials and Methods We performed a prospective, multicenter cohort study including Brugada patients with at least one available type 1 ECG (either spontaneously or drug-induced) between January 2005 and November 2021. Paper ECG were first digitized and then automatically analyzed using the Glasgow and Bravo algorithms (included in the logiciel CalECG). Clinical data and Brugada related events at diagnosis and during follow-up were collected. Sudden cardiac death, aborted cardiac arrest and appropriate ICD therapy in the VF zone were considered as major events. The predictive value of clinical and ECG parameters for symptomatic status was assessed using uni- and multivariate Cox models. Results ECGs from 301 Brugada patients (77% male, mean age at diagnosis 43 years, follow-up 7±5.6 years) were analyzed. Brugada-related symptoms (cardiac syncope or major event) occurred in 23% of patients before diagnosis and 11% during follow-up (incidence: 1.57%/year). After multivariate Cox analysis, only 2 baseline ECG (without Ajmaline) parameters were significantly associated with major events: RR interval (HR=1.01 (95%CI [1-1.01]), p=0.002) and QRS duration in lead V1 (HR=1.04 (95%CI [1-1.07]), p=0.038). QRS prolongation in lead V1 >113 ms (AUROC 0.69 (95% CI [0.58-0.8])) was associated with a 3-fold increased risk of major event (HR =3.49 (95% CI [1.72-7.09]), p=0.001). Conclusion Many previously described ECG parameter were not associated with major event in Brugada patients after multi-parameter evaluation. Sinus rate and QRS duration on lead V1 were independent risk factor. These results need to be validated on an external cohort. The predictive value of ECG parameters in Brugada syndrome should be assessed using automated multiparametric quantification.

Background: Conflicting data exist regarding the benefit of urgent coronary angiogram and percutaneous coronary intervention (PCI) after sudden cardiac arrest, particularly in the absence of ST-segment elevation. We hypothesized that the type of lesions treated (stable versus unstable) influences the benefit derived from PCI. Methods: Data were taken between May 2011 and 2014 from a prospective registry enrolling all sudden cardiac arrest in Paris and suburbs (6.7 million inhabitants). Patients undergoing emergent coronary angiogram were included. Decision to perform PCI was left to the discretion of local teams. We assessed the impact of emergent PCI on survival at discharge according to whether the treated lesion was angiographically unstable or stable, and we investigated the predictive factors for unstable coronary lesions. Results: Among 9265 sudden cardiac arrests occurring during the study period, 1078 underwent emergent coronary angiogram (median age: 59.6 years, 78.3% males): 463 (42.9%) had an unstable lesion, 253 (23.5%) only stable lesions, and 362 (33.6%) no significant lesions. Emergent PCI was performed in 478 patients (91.4% of unstable and 21.7% of stable lesions). At discharge, PCI of unstable lesions was associated with twice-higher survival rate compared with untreated unstable lesions (47.9% versus 25.6%, P =0.013), while stable lesions PCI did not improve survival (25.5% versus 26.3%, P =1.00). After adjustment, PCI of unstable coronary lesions was independently associated with improved survival (odds ratio, 2.09 [95% CI, 1.42–3.09], P P =0.824). Angina, initial shockable rhythm, ST-segment elevation, and absence of known coronary artery disease were independent predictors of unstable lesions. Conclusions: Emergent PCI of unstable lesions is associated with improved survival after sudden cardiac arrest, contrary to PCI of stable lesions. Accordingly, early PCI should only be performed in patients with unstable lesions. Four factors (chest pain, ST-elevation, absence of coronary artery disease history, and shockable initial rhythm) could help identify patients with unstable lesions who would, therefore, benefit from emergent coronary angiogram.

We report a child with Beckwith-Wiedemann syndrome (BWS) as the consequence of an apparently balanced, maternally inherited reciprocal translocation t(11;17)(p15.5;q21.3). His mother and aunt, who inherited the translocation from their father, did not have BWS. At birth, long QT syndrome (LQTS) was diagnosed in this child and, secondarily, among apparently healthy family members carrying the translocation. By FISH analysis, the breakpoint in 11p15.5 interrupts the KCNQ1 gene between exons 2 and 10 and causes a loss of methylation of the IC2 (and thus BWS) on the maternally inherited der(11) chromosome. To explain the presence of LQTS segregating with the t(11;17) translocation in this family, we hypothesize that the translocation that interrupts KCNQ1 allow translation of an abnormal short allele that interferes in a dominant negative way with the normal isoform 1 of KCNQ1 in the heart (where this allele is not subject to parental imprint). This appears to be the first report of BWS with congenital LQTS, which should be considered as a rare but serious complication to be searched systematically in patients with BWS due to 11p15 rearrangements.

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.

Resume L'âge comporte ses specificites rythmologiques : chez le nouveau-ne et le nourrisson, les flutters ont une frequence particulierement rapide (400/min). Apres reduction, ils guerissent sans recidive apres l'âge de 1 an. Les tachycardies atriales chaotiques s'accompagnent de foyers auriculaires multiples, de brefs lambeaux de flutter ou de fibrillation. Elles guerissent definitivement en quelques mois. Les tachycardies hisiennes sont graves, mais leur frequence propre se ralentit progressivement sous amiodarone en quelques annees. Les rythmes reciproques paroxystiques du nourrisson ont une frequence elevee (300/min). La decompensation cardiaque est rapide en l'absence de traitement. La plupart d'entre eux guerissent avant l'âge de 1 an. Les syndromes de preexcitations ventriculaires doivent etre explores avant la puberte en vue de l'ablation des voies accessoires a periode refractaire courte. Les arythmies chroniques primitives de l'enfant exposent au risque de myocardiopathie rythmique secondaire : qu'il s'agisse de rythme reciproque permanent (a RP' long), de tachycardie atriale chronique ou de forme plus rare de tachycardie ventriculaire, leur pronostic lointain est globalement favorable au prix d'un traitement medical prolonge, poursuivi jusqu'a la guerison spontanee ou l'ablation du trouble du rythme par radiofrequence. Les arythmies ventriculaires paroxystiques sont graves et exposent au risque de mort subite : qu'il s'agisse des syndromes du QT long, des tachycardies ventriculaires catecholergiques ou du syndrome de Brugada, ces arythmies ont beneficie des progres recents de la biologie moleculaire et d'une meilleure comprehension des pathologies des canaux ioniques. L'enquete genetique familiale s'impose apres la decouverte d'un cas index. La prevention de la mort subite repose essentiellement sur les s-bloquants et le defibrillateur implantable. Le pronostic de blocs auriculoventriculaires complets congenitaux s'est considerablement ameliore avec la mise en place preventive d'un stimulateur cardiaque. L'hyperreactivite vagale et ses liens possibles avec la mort subite du nourrisson font l'objet de debats.

Arrhythmias in neonates and infants require a specific management due to the particular nature of the rhythm anomalies in children. Accurate diagnosis of the tachycardia is realised mainly by means of ECG recording and vagal manoeuvres. The nature of the tachycardia will determine management, therapy and prognosis. In neonates 440 ms) and a high risk of syncope and sudden death due to malignant ventricular arrhythmias. Beta-blockers significantly decrease cardiac events during follow-up. Congenital atrio-ventricular block is rare but potentially lethal in the first months of life in the absence of permanent pacing. The morbidity remains high during long term follow-up in unpaced children.

Resumen El sindrome del QT largo congenito (SQTL), clinica y geneticamente heterogeneo, se caracteriza por un alargamiento del intervalo QT en el electrocardiograma (ECG), asociado a un riesgo de trastornos graves del ritmo ventricular (torsades de pointes, fibrilacion ventricular), que pueden provocar sincopes y muerte subita. Este sindrome familiar raro, transmitido segun distintos modos mendelianos, se manifiesta en sujetos cuyos examenes morfologicos cardiacos habituales son normales. La potencial gravedad del pronostico justifica la deteccion sistematica de los sujetos afectados. El origen genetico de la enfermedad ha podido ser confirmado, habiendose identificado hasta la fecha al menos seis loci y cinco genes y constituye un ejemplo tipico de los trastornos del ritmo ventricular adrenergico. El tratamiento se basa en los β-bloqueantes, particularmente para todas las formas sintomaticas. El tratamiento es igualmente preventivo, ya que se debe evitar cualquier medicamento que pueda alargar la duracion del intervalo QT en todos los sujetos portadores de una anomalia genetica. En caso de sospecha de SQTL, es imprescindible llevar a cabo un ECG con registro Holter y la determinacion del genotipo en todos los miembros de la familia directa, para poder identificar a los pacientes portadores de la mutacion que todavia son asintomaticos.

Junctional ectopic tachycardia (JET) is a rare cardiac arrhythmia characterized by atrio-ventricular dissociation, a high rate junctional escape rhythm and poor clinical tolerance in neonates and infants. Sudden infant death has been reported. The intra-uterine presentation of this arrhythmia is unknown. We report a familial form of JET with antenatal diagnosis. A sustained tachycardia at a rate of 170 beats/min with a 1:1 conduction was diagnosed in a hydropic fetus at a gestational age of 32 weeks. The older brother had presented with prenatal hydrops and junctional ectopic tachycardia was diagnosed at birth. Assuming that this arrhythmia was a JET, amiodarone was given to the mother in order to control the fetal tachycardia. The arrhythmia persisted with a 1/1 pattern but at a slower ventricular rate (140 beats/min). The ECG performed at birth revealed a narrow QRS tachycardia with a ventricular rate of 180 beats/min and a 1/1 retrograde conduction. Amiodarone therapy was continued with the addition of propanolol. Postnatal echocardiography revealed normal chambers and left ventricular dysfunction with a left ventricular shortening fraction of 17 per cent. Subsequent ECGs and Holter monitoring demonstrated typical electrocardiographic features of JET. Both parents had a normal ECG and Holter monitoring. A fetal tachycardia of moderately high rate with a 1/1 retrograde conduction and poor cardiac tolerance can be due to JET. In such cases, the use of amiodarone can be considered as a first line drug.

To assess the cardiac and extracardiac safety and efficacy of flecainide versus propafenone in patients suffering from episodes of paroxysmal atrial fibrillation (AF) or atrial flutter, 97 patients were enrolled in a randomized, open-label, long-term, parallel, comparative multicenter study. The diagnosis of paroxysmal AF or atrial flutter had to be fully documented prior to inclusion in the study. Of the 97 patients enrolled in the study, 48 patients (25 men, 23 women, mean age 62.4 +/- 12.3 years) received flecainide; 49 patients (26 men, 23 women, mean age 63.6 +/- 12.2 years) received propafenone. The initial dose of flecainide was 50 mg twice daily, and this could be increased in steps of 50 mg twice daily every 4 days to a maximum of 300 mg/day. The initial dose of propafenone was 300 mg twice daily and this could be increased in steps of 300 mg every 4 days to a maximum of 1200 mg/day. At each visit, medical events, vital sign measurements (blood pressure, pulse rate), concomitant medications, adverse experiences, and study drug dosage changes were evaluated. Routine clinical laboratory tests were evaluated at the month 6 visit, and a 24-hr Holter recording was obtained at the month 1 visit. Almost half (45) of the patients were discontinued from the study before completing 1 year of therapy. The probability of successful treatment versus time--i.e., the proportion of patients who remained on therapy over the course of 1 year therapy--was 0.619 for the flecainide group and 0.469 for the propafenone group (p = 0.079; difference not significant). The difference is largely attributed to the higher proportion of patients in the propafenone group (9) than in the flecainide group (2) who experienced side effects important enough to stop the treatment. (The incidence of side effects was not statistically different between treatment groups, although it was higher in the propafenone group.) The proportion of patients who discontinued treatment due to inadequate response was similar in the 2 groups: 11 patients (22.9%) in the flecainide group and 12 patients (24.4%) in the propafenone group withdrew from the study, primarily because of an inadequate response, i.e., they experienced an increase in duration, frequency, and severity of attacks of AF or atrial flutter. Neurologic signs, central and peripheral, were mostly encountered in the flecainide group (8.5%), and, gastrointestinal effects were more often reported in the propafenone group (16.7%). In paroxysmal AF and paroxysmal atrial flutter, flecainide and propafenone are equally effective. However, in this study the probability of a patient's staying on flecainide after 1 year had a tendency to be higher than the probability of staying on propafenone, due to a greater proportion of secondary effects with propafenone.

We report a child with Beckwith-Wiedemann syndrome (BWS) as the consequence of an apparently balanced, maternally inherited reciprocal translocation t(11;17)(p15.5;q21.3). His mother and aunt, who inherited the translocation from their father, did not have BWS. At birth, long QT syndrome (LQTS) was diagnosed in this child and, secondarily, among apparently healthy family members carrying the translocation. By FISH analysis, the breakpoint in 11p15.5 interrupts the KCNQ1 gene between exons 2 and 10 and causes a loss of methylation of the IC2 (and thus BWS) on the maternally inherited der(11) chromosome. To explain the presence of LQTS segregating with the t(11;17) translocation in this family, we hypothesize that the translocation that interrupts KCNQ1 allow translation of an abnormal short allele that interferes in a dominant negative way with the normal isoform 1 of KCNQ1 in the heart (where this allele is not subject to parental imprint). This appears to be the first report of BWS with congenital LQTS, which should be considered as a rare but serious complication to be searched systematically in patients with BWS due to 11p15 rearrangements.

A 4-year-old girl was seen in the pediatric emergency department because of a first generalized tonic-clonic seizure that occurred at school. The seizure was preceded by a sudden, prolonged attack of unconsciousness, lasted 5 minutes, and was followed by drowsiness. The parents were first cousins of Algerian descent. She had an unremarkable family history. Pregnancy and delivery were uneventful. At age 4, she underwent bilateral cochlear implantation for congenital sensorineural deafness. Neurologic examination was notable for deafness and marked agitation, which was reported to be usual by her parents. Psychomotor development was mildly delayed. ### Questions for consideration: 1. What is your evaluation of this first nonfebrile seizure? 2. Would you prescribe a treatment and, if so, which one? GO TO SECTION 2 When a child is evaluated for a probable first seizure, it is important to assess if it was really a seizure and if it was really a first attack. There is currently no test that proves that a seizure occurred. About half of the children with a presumed first seizure have had a prior unrecognized seizure.1 In our patient, it was the first …

To describe the management of patients with atrial fibrillation (AF) and to study consistency with guidelines on management of AF.Observational study on a random sample of cardiologists from a French national database. Each cardiologist had to recruit the first five patients meeting inclusion criteria (patients diagnosed with AF between January 2004 and one month before inclusion and accepting the collection of their medical data).Between December 2006 and January 2207, 1789 patients aged 71 on average have been recruited by 481 cardiologists. Fifty-one percent were diagnosed with paroxysmal, 15% with persistent and 33% with permanent AF. Restoration of sinus rhythm was preferred in forms considered as paroxysmal or persistent forms whereas control of the ventricular rate was more frequent in AF considered as permanent. Overall, therapeutic guidelines are applied in practice, despite a frequent use of amiodarone in patients with no associated heart disease. Prevention of thromboembolism was observed in 88% of the patients.FACTUEL is the biggest observational study on AF ever conducted in France. The therapeutic strategies used by the cardiologists are consistent with the objectives of preventing thromboembolism and controlling heart rhythm and/or rate. In most cases, the treatment used is consistent with the therapeutic guidelines.

The trough concentration-dose (C/D) ratio of flecainide was prospectively studied in 78 patients with various cardiac arrhythmias. After the removal of two outlier values, no influence of body weight on C/D ratio was evidenced. Coadministration of amiodarone, and, moreover, the presence of heart failure increase the C/D ratio, from 2.01 +/- 0.78 to 2.55 +/- 0.37 and 2.9 +/- 1.19 ng/ml/mg, respectively (p less than 0.001 by two-factor analysis of variance). The presence of both heart failure and amiodarone therapy increases the C/D ratio to 3.88 +/- 1.07 ng/ml/mg. A single loading oral dose (30 mg/kg) of amiodarone increased C/D measured at the sixth hour in nine patients from 2.27 +/- 0.50 to 2.57 +/- 0.73 ng/ml/mg (p less than 0.05). The trough C/D ratio increased more during chronic treatment from 2.03 +/- 0.86 to 2.92 +/- 1.32 ng/ml/mg (p less than 0.05). Thus, a dosage reduction of flecainide (of 50% in some cases) is mandatory, in case of heart failure or the combination with amiodarone therapy, to obtain a plasma level of the drug that is similar to those observed in patients with a normal heart and without amiodarone therapy. The flecainide-amiodarone interaction seems time dependent.

In case of an accessory pathway, children are exposed to severe cardiac events including sudden death. Radiofrequency ablation is a standardized procedure, which can be applied to a significant number of children although complications can still potentially occur. In this context, transesophageal evaluation of the accessory pathway evaluation can be discussed.Among 140 procedures performed in 19 years, 70 were done for accessory pathway evaluation. The preexcitation was overt in 59 children older than 5 years, which form the basis in this study.Anterograde refractory period was determined in 88% cases and was found220 ms in 12 cases justifying an ablation procedure. Conversely, in case of a long refractory period (250 ms), the ablation procedure was not performed in 8 asymptomatic cases and was postponed in 11/20 mildly symptomatic children. Transesophageal electrophysiologic study seems legitimate in asymptomatic or mildly symptomatic children.This technique is probably less useful in case of an overt preexcitation and recurrent reciprocating tachycardia requiring long-term antiarrythmic treatment. In this case, endocavitary electrophysiological study eventually followed by an ablation procedure seems the best option.

The clinical syndromes responsible for sudden death have benefited from spectacular advances in recent years. The authors propose a brief review of the genetic, electrophysiological, physiopathological and clinical characteristics of the long QT syndrome, Brugada's syndrome, adrenergic ventricular tachycardias and the short QT syndrome. The initial concept of one gene responsible for one pathology has uncovered new zones of complexity within diseases considered to be monogenetic in origin. These new findings have impacted on diagnostic and therapeutic strategies of these conditions. However, the assessment of the arrhythmic risk and the choice of treatment in individual cases still remain almost exclusively the domain of clinical judgement. Similarly, the better understanding of the mechanisms of the arrhythmias in these syndromes has opened up new specific therapeutic approaches which require validation by clinical trial.

Arrhythmias in neonates and infants require a specific management due to the particular nature of the rhythm anomalies in children. Accurate diagnosis of the tachycardia is realised mainly by means of ECG recording and vagal manoeuvres. The nature of the tachycardia will determine management, therapy and prognosis. In neonates3 months, supraventricular tachycardia due to Wolff-Parkinson-White syndrome represents 70% of all supraventricular tachycardias, which, after conversion by vagal manoeuvres, requires a preventive treatment by digoxine (10 y/kg/day tid). Neonatal flutter occurs in infants without structural heart disease. It has an excellent prognosis after conversion to sinus rhythm by transoesophageal pacing. Atrial tachycardia is less frequent but can induce a tachymyocardiopathy and often requires combined therapy including amiodarone. Long QT syndrome, clinically and genetically heterogeneous, is characterized by a prolongation of the QT interval (QTc440 ms) and a high risk of syncope and sudden death due to malignant ventricular arrhythmias. Beta-blockers significantly decrease cardiac events during follow-up. Congenital atrio-ventricular block is rare but potentially lethal in the first months of life in the absence of permanent pacing. The morbidity remains high during long term follow-up in unpaced children.

Bidirectional tachycardias are rare arrhythmias. Nevertheless in the sixties and seventies these arrhythmias prompted much work relating to their mechanism. Discussions about the supposed supra-ventricular origin of certain bidirectional tachycardias essentially rested on presumptive arguments based on electrocardiographic analysis. All the electrophysiological investigations which could be performed in tachycardia showed a ventricular origin. The current hypotheses concerning the electrophysiological mechanism favour non-unifocal mechanisms as well as a very diverse aetiology: an automatic focus, or the triggered activities being associated with alternating conduction, or re-entry between the left hemibranches. Although the classic context is of excess digitalis with advanced cardiopathy, readily in atrial fibrillation with a poor prognosis as a corollary, the most recent description of catecholergic ventricular tachycardias with the very characteristic appearance of bidirectional tachycardias justifies updating the understanding of these unusual tachycardias.

The neonatal congenital long QT syndrome (LQTS) is rare and of bad prognosis due to the presence of severe ventricular arrhythmia and conduction abnormalities.we included 24 propositus newborns from our population with LQTS. Genetic study was possible in 19 cases.the diagnosis of LQTS was made according to a QT prolongation associated with a sinusal neonatal bradycardia (n=9) or a 2/1 AV block (n=15). The onset presentation consisted of syncope (n=2), torsades de pointes (n=7), cardiovascular collapse (n=5), cardiac arrest (n=1). The mean QTc was at 550+60 ms. During the neonatal period the treatment consisted of beta-blocking agents in all cases, associated with a definitive pacemaker implantation in 10 cases with 2/1 AV block. Three newborns with a 2/1 AV block died during the first month of life (one case due to a septecemia after implantation of a pacemaker, and two who were waiting for that implantation). All survivors remained asymptomatic during a follow-up period of 7 years. In all cases with a 2/1 AV block we identified mutations in HERG (n=8). Newborns with isolated sinusal bradycardia presented all a mutation in KCNQ1 (n=9).the LTQS with 2/1 AV block is preferably associated with mutation in HERO with a bad initial prognosis.

The Brugada syndrome is characterised clinically by the occurrence of syncope or sudden death due to ventricular arrhythmias in patients with structurally normal hearts and electrocardiographic signs of right bundle branch block and ST elevation in the right precordial leads (V1 to V3). The transmission of the condition is autosomal dominant with variable penetration. Mutations have been identified in a gene coding for the alpha sub-unity of the sodium channel (SCN5A) on chromosome 3 in only 30% of cases. This mutation is responsible for a reduction of the density of the sodium current and explains the aggravation of the electrocardiographic anomalies by antiarrhythmic drugs which block the sodium channels. The prognosis is poor in symptomatic patients and depends on the prevention of sudden death by the implantation of an automatic defibrillator. The therapeutic decision is much more difficult in asymptomatic patients without a family history. The authors propose a decisional algorithm. The management may have to be modified in the months or years to come depending on advances in the understanding of this syndrome.

The congenital long QT syndrome (LQTS) is a variable clinical and genetic entity characterised by prolongation of the QT interval on the ECG associated with the risk of serious ventricular arrhythmias (torsades de pointe, ventricular fibrillation) which may cause syncope and sudden death in patients with otherwise normal hearts. To date, 6 loci have been identified with the genes responsible for the forms LQT1, LQT2, LQT5 and LQT6, coding for the potassium channels (KCNQ1, HERG, KCNE1 and KCNE2, respectively) which, in the heterozygote state, are responsible for the main forms of LQTS without deafness and, in the homozygote state (KCNQ1 and KCNE1) for the recessive forms of LQTS with or without deafness. The gene for the LQT3 form codes for the cardiac sodium channel (SCN5A). The genetic variability observed in the LQTS corresponds to the diversity of cardiac ionic channels implicated in the genesis of the action potential, so making the LQTS a disease of the ionic channels or a "channelopathy". The potential severity of the prognosis justifies testing of subjects with long QT intervals on the ECG and Holter recording. In order to identify subjects with the genetic abnormality who are asymptomatic, these investigations associated with genetic testing should be made in all close members of the family of an affected person. The major problem remains the evaluation of the risk of sudden death in asymptomatic subjects with a genetic abnormality. At present, in the absence of clearly proven prognostic factors and in the knowledge that effective treatment without major secondary effects is available, all patients should be given prophylactic betablocker therapy.

Prone sleep position is obviously the main risk factor for sudden infant death. Other risk factors, such as vagal overactivity particularly in the familial form, are still discussed. We here report 15 families characterized by the coexistence of vagal overactivity and sudden infant death. At least, 1 child for each family had documented [Holter or occulo-cardiac reflex (OCR)] vagal overactivity. In 5 families 2 children were affected; in 2 families 3 children were affected and in 1 family 4 children were affected. Sudden death occurred in the elderly of the family in 8 cases, in the twin in 3 cases, in the 2nd in 3 cases and in the 5th child in 1 case. Within the 15 families, at least 1 parent had experienced vagally-induced fainting or syncope in 10 cases. Familial pattern of vagal overactivity is underlined. Possible links between vagal overactivity, risk factor for suddden death and sudden death are discussed. We suggest an Holter-ECG and OCR follow-up for sudden infant death siblings with history of familial vagal overactivity (3 examinations during the 1st year of life, at 1, 3 and 9 months).

Long QT syndrome is characterized by a prolongation of the QT interval on the surface ECG. This clinically and genetically heterogeneous cardiac disease is potentially lethal due to ventricular polymorphic tachyarrhythmias leading to syncope or sudden death. It is transmitted according to different mendelian modes due to mutations in several genes coding for cardiac ion channels. Heterozygous mutations in KCNQ1, HERG, SCN5A, KCNE1 and KCNE2 genes are responsible for the dominant form without deafness whereas homozygous mutations in KCNQ1 and KCNE1 are responsible for the recessive form (Jervell and Lange-Nielsen syndrome) associated with congenital deafness. We report the case of a 5 year-old boy referred for syncope with a prolongation of the QTc interval (526 ms) and a 2/1 Atrio-Ventricular (AVB) block on the surface ECG. Under beta-blocking therapy, the sinus rate decreased and the 2/1 AVB disappeared. Electrophysiological study evidenced an infra-hisian block and a unipolar ventricular endocardial pacemaker was implanted. A V1777M missense mutation was identified in the C-terminal part of SCN5A, cardiac sodium channel gene, at the homozygous state in the proband and at the heterozygous state in both parents and 2 sibblings. Only the proband had a severe phenotype with syncope and AV conduction anomalies. All other genetically affected subjects were asymptomatic. This study provides evidence for the involvement of homozygous LQT3 forms in "functional" AVB.

Atrial fibrillation is not a homogenous entity. Numerous parameters affect its cause, its continuation, and the arrest of an attack. The presence or absence of cardiopathy and left ventricular dysfunction play a major role via the electrophysiological and haemodynamic consequences and the repercussions on the state of the autonomic nervous system, and finally on the effect of anti-arrhythmics themselves. This shows the importance of taking into account all of these parameters together in order to adapt the therapeutic approach. Equally, this underlines the difficulty in interpreting clinical studies comparing pharmacological treatments when the populations treated are poorly defined or very heterogenous. Most often, one drug is not more or less effective than another, it is more or less suited to the patients treated. The frequency of recurrences of AF despite anti-arrhythmic treatment (on average 50% to 60% at one year) means that in paroxysmal AF the goal of anti-arrhythmic treatment is relatively modest: essentially reducing the frequency, duration and severity of AF attacks, allowing an improvement in the quality of life. The consequences in daily practice are clear: one must ensure good patient compliance and minimise the risks of treatment: side effects of and pro-arrhythmic effects of anti-arrhythmics.

The authors report two cases of foetal supraventricular tachycardia in healthy hearts with 1/1 atrioventricular conduction which turned out to be atrial tachycardias in the postnatal period. The first foetus had permanent tachycardia at 190/minute at 34 weeks' amenorrhea with left ventricular dysfunction at 36 weeks. In the postnatal period, treatment with digoxine and amiodarone restored sinus rhythm and normal left ventricular function. Permanent foetal tachycardia, even at a rate of less than 200 beats/minute, should suggest an arrhythmia and may lead to left ventricular dysfunction in utero. The other foetus had an aneurysm of the foramen ovale with paroxysmal tachycardias at 220/minute without cardiac dysfunction. A Holter at 1 month showed paroxysmalatrial tachycardia. Postnatal rhythm monitoring is necessary in paroxysmal foetus tachycardia, especially with prenatal aneurysm of the foramen ovale.

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, p0.01). Grade 1 appearances were observed more often in LQT2 (18 vs 8% for LQT1 and 4% for controls, p0.01). 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.

Cardiac complications are common in adolescent anorexia nervosa and are the cause of a third of deaths. Some workers have reported prolongation of the QT interval and cases of sudden death in these patients. The aim of this study was two-fold: to assess the cardiac complications of anorexic adolescents and to determine the outcome after renutrition in the hospital setting. This was a prospective study of 48 consecutive cases (45 girls) with an average age of 14 +/- 2 years, admitted to the paedopsychiatric unit and fulfilling the DSM-IV criteria of anorexia nervosa. The digitised ECG, Holter ECG and echocardiography were recorded before and after renutrition. Anorexia nervosa was severe with a body mass index14 in 2/3 of cases. Over 2/3 of patients had bradycardia with a heart rate50/min in half the cases but normal chronotropic function on Holter monitoring. Prolongation of the QTc interval was demonstrated (QTc440 ms in 11/44 cases). Echocardiographic abnormalities, in particular left ventricular dysfunction (24/46) and pericardial effusion (12/46) were reversible after renutrition. There were no clinical or biological predictive factors for the occurrence of cardiac complications on admission. The authors confirm that cardiac complications of anorexia nervosa are common, usually benign and always reversible after renutrition in hospital. Therefore, most electrical abnormalities normalise with the heart rate and echocardiographic abnormalities with improvement of conditions of load.

Long QT syndrome (LQTS) is a clinically and genetically heterogenous syndrome characterized by a lengthening of the QT interval on the surface ECG and a propensity to severe ventricular arrhythmias such as torsades de pointes and ventricular fibrillation, leading eventually to syncope and sudden death. This rare syndrome with a mendelian inheritance occurs in subjects with otherwise normal cardiac morphological examination. The potentially severe prognosis justifies a presymptomatic diagnosis. The genetic nature of the disease has been confirmed with the identification of at least six loci and five genes. This syndrome is a perfect illustration of an adrenergic-induced ventricular arrhythmia. The first-line treatment is a beta-blocking agent for all symptomatic patients. In addition, a number of drugs known to lengthen ventricular repolarization must be prohibited. In case of suspicion of LQTS, all family members should be tested both clinically with a surface ECG and genetically in order to diagnose presymptomatic patients.

The identification of patients at high risk of sudden cardiac death is one of the greatest challenges for cardiologists. Non-invasive methods have, characteristically, low predictive sensitivities and specificities. The role of abnormalities of ventricular repolarisation (QT interval) in the genesis of ventricular arrhythmias has been well established by experimental data. For this reason, parameters of ventricular repolarisation on the surface electrocardiogram have been proposed. However, taken in isolation, these markers are limited in terms of arrhythmic risk stratification. This report analyses the value of the different parameters of ventricular repolarisation in the identification of high risk: QT dispersion, QT dynamics and T wave alternans. The dispersion of the QT interval is a marker of unhomogenous ventricular depolarisation. This concept must be applied differently in such pathologically dissimilar diseases such as myocardial infarction, cardiomyopathy or the long QT syndrome. Moreover, methodological problems make the interpretation of many experimental studies very delicate. Frequency dependence of the QT helps select high risk patients after myocardial infarction or with dilated cardiomyopathy. A common feature of pathological ventricular myocardium is the more pronounced frequency-dependency of the QT interval. The predictive value of this new index should be evaluated and compared with other non-invasive risk factors in prospective trials. Studies of T wave alternans in selected high risk populations, essentially patients with coronary artery disease and dilated cardiomyopathy, have shown this parameter to be predictive of arrhythmia. The predictive value requires confirmation in much larger populations at lower levels of risk of arrhythmia and sudden death in prospective trials. A new field of research has opened up in the study of ventricular repolarisation. Many studies have been undertaken on the duration of the QT interval, the morphology of the QT (including T wave alternans and post-pause changes) and, finally, the dynamics of the QT interval. By regrouping, analysing and using these data correctly, we should be able to identify new markers of high arrhythmic risk.

The possibility of reversible cardiac asystoly due to paroxysmal vagal overactivity (VO) has been well studied, first in adults, then in children, and finally in breath-holding spells. Few studies deal with infants and the incidence of VO among preterm, apparent life-threatening event (ALTE) and sudden infant death syndrome (SIDS). In this review, we summarize data acquired during the past 20 years leading to the diagnosis of VO in infants. We describe the clinical aspects of VO in infants and young children such as Holter-ECG and oculocardiac reflex criteria. The familial aspect of VO and its possible link with SIDS (a new risk factor?) are discussed. Finally, whether or not to treat infants with symptomatic VO is discussed.

In cases of permanent tachycardia, ante-natal diagnosis of chronic reciprocating rhythms with long RP' intervals or His bundle tachycardias is difficult. The authors report two cases of permanent foetal tachycardia with 1/1 atrioventricular conduction. In one case, the tachycardia rate was 170/min with anasarca treated by amiodarone in view of a family history of His bundle tachycardia. In the other case, the tachycardia rate was 200/min but with no signs of cardiac failure and was, therefore, not treated. The ECG at birth confirmed the diagnosis of His bundle tachycardia in the first case and identified a chronic reciprocating rhythm in the other.

The congenital long QT syndrome is characterised by the presence of syncopes due to torsades de pointe which may degenerate to ventricular fibrillation and cause sudden death. These syncopes occur in young subjects with electrocardiographic abnormalities and prolongation of the QT interval. Patients with the autosomally dominant transmitted Romano-Ward syndrome with normal audition are classically opposed to those with the Jervell and Lange-Nielsen autosomally recessive syndrome who have bilateral total deafness. Our understanding of the congenital long QT syndrome has improved in recent years with respect to the physiopathology, diagnosis and treatment, due to research in the fields of genetics, electrocardiography and electrophysiology. The diagnosis is based on analysis of the phenotype and genotypes. A family enquiry is always necessary to detect unrecognised forms. Five culprit genes have been identified for the Romano-Ward syndrome. All code for subunits of sodium or potassium channels: two a subunits of the potassium channels (QVLQT1 for LQT1, HERG for LQT2), the a subunit of the sodium channel INa (SCN5A for LQT3), and two regulatory subunits of potassium channels (KCNE1 for LQT5 regulating the KvLQT1 channel and MiRP1 regulating HERG). The concept of genetic heterogeneity of the congenital long QT syndrome may thus be understood: different genes may be responsible for the same phenotype. Except for specific cases, the usual treatment is life-long betablocker therapy and the avoidance of a large number of drugs, the list of which is continually updated. A multicentre trial is underway to validate betablocker therapy for the prevention of cardiac events in a LQT1 genotype population. Prospective studies will be necessary to assess gene-specific treatments.

Junctional ectopic tachycardia (JET) is a rare cardiac arrhythmia characterized by atrio-ventricular dissociation, a high rate junctional escape rhythm and poor clinical tolerance in neonates and infants. Sudden infant death has been reported. The intra-uterine presentation of this arrhythmia is unknown. We report a familial form of JET with antenatal diagnosis. A sustained tachycardia at a rate of 170 beats/min with a 1:1 conduction was diagnosed in a hydropic fetus at a gestational age of 32 weeks. The older brother had presented with prenatal hydrops and junctional ectopic tachycardia was diagnosed at birth. Assuming that this arrhythmia was a JET, amiodarone was given to the mother in order to control the fetal tachycardia. The arrhythmia persisted with a 1/1 pattern but at a slower ventricular rate (140 beats/min). The ECG performed at birth revealed a narrow QRS tachycardia with a ventricular rate of 180 beats/min and a 1/1 retrograde conduction. Amiodarone therapy was continued with the addition of propanolol. Postnatal echocardiography revealed normal chambers and left ventricular dysfunction with a left ventricular shortening fraction of 17 per cent. Subsequent ECGs and Holter monitoring demonstrated typical electrocardiographic features of JET. Both parents had a normal ECG and Holter monitoring. A fetal tachycardia of moderately high rate with a 1/1 retrograde conduction and poor cardiac tolerance can be due to JET. In such cases, the use of amiodarone can be considered as a first line drug.

The congenital long QT syndrome (QTL) is a heterogenic clinical and genetic entity characterised by prolongation of the QT interval which may be complicated by syncope and sudden death. Four genes have been identified for the cardiac potassium (KCNQ1, HERG and KCNE1) and sodium (SCN5A). The aim of this study was to assess the prognosis of the disease by the site of mutation identified on the morbid gene. Thirty-two genotyped families participated to this study. Each subject gave a clinical history, an ECG and a search for genetic mutation. Eighteen mutations in the transmembrane domains of KCNQ1 were identified in 25 families and 2 mutations in the C-terminal part were found in 4 families. The phenotype was less severe in C-terminal part mutations: less syncopes and sudden deaths (22 vs 55%, p0.001) and a shorter QTc (458 +/- 31 ms vs 479 +/- 31 ms, p = 0.0003). Three mutations were detected in the C-terminal part of HERG in 3 different families. Their phenotype was less severe with syncoped related to hypokalemia. The authors also report the case of a family in which two subjects who were the most severely affected had two mutations, one in HERG and the other in KCNQ1. This study confirms the value of a genetic research in assessing the severity of the congenital long QT syndrome.

Tachycardias arise from an arrhythmogenic substrate and a trigger factor, an extrasystole, the two factors being under the influence of the autonomic nervous system. The study of the mechanisms of spontaneous initiation of arrhythmias must, therefore, take these three factors and their interactions into account. The frequency dependency of an arrhythmia and the sensitivity of the substrate to the adrenergic system varies with time in a given subject and from one patient to another according to the presence and type of cardiac disease. The mode of initiation of most ventricular tachycardias and the therapeutic consequences may be understood: in some forms of cardiac disease, such as arrhythmogenic right ventricular dysplasia, the increase in heart rate which usually precedes sustained ventricular arrhythmias is only perceptible in mild or recent forms, unlike the more chronic dysplasias. This suggests that the arrhythmogenic substrate becomes more sensitive to catecholamines with time, and therefore requires smaller changes in sympathetic tone in order to be expressed (adrenergic paradox). Heart rate changes accompany modifications of sinus variability. Holter monitoring has shown, and this has been confirmed by recordings obtained from patients with implanted automatic defibrillators, that global sinus variability decreases before the initiation of a ventricular arrhythmia. Studies of the dynamics of ventricular repolarisation should also confirm the changes of QT frequency-dependency. The analysis of the initiation of arrhythmias would only have an academic interest if this was limited to a purely descriptive exercise. It is one of the best means of understanding arrhythmias and their therapeutic implications. The development of computerised methods of analysis of Holter monitoring should lead to further progress in this field.

The aim of the study was to evaluate cardiorespiratory exercise tolerance in asymptomatic children with Ebstein's anomaly. Eleven children with a mean age of 9.6 years were prospectively studied by spirometry, cardiopulmonary exercise testing (bicycle ergometer n = 8, treadmill test n = 3), and contrast echocardiography. A right-to-left atrial shunt was detected by contrast echocardiography in 7 children (group 1), whereas no shunt was found in 4 (group 2). VO2 max was decreased [84.5 (SD = 16.8)] and was strongly correlated to oxygen saturation in group 1 (p0.0001). Oxygen saturation at peak uptake was significantly decreased compared to baseline [97.4 (SD = 2.0) vs 90% (SD = 9.5%), p = 0.02] and was significantly lower in group 1 than in group 2 [85.7 (2.2) vs 98.2% (SD = 1.2%), p = 0. 03]. Oxygen desaturation was related to a right-to-left atrial shunt (p = 0.01). Decreased VO2 max was also correlated to the small size of the left ventricle (p = 0.05). We concluded that decreased exercise tolerance in children with asymptomatic Ebstein's anomaly is related to a right-to-left atrial shunt and to a small left ventricle. In case of poor exercise tolerance, a contrast echocardiography should be performed to detect an atrial septal defect.

SEVERAL FORMS: Congenital long QT syndrome is a clinically (with and without deafness) and genetically (recessive or dominant autosomal inheritance) heterogeneous entity characterized by a long QT interval on the ECG associated with the risk of severe ventricular arrhythmia (torsade de pointes, ventricular fibrillation) and subsequent syncope or sudden death.This rare familial syndrome is transmitted by different modes of inheritance and occurs in subjects with a morphologically normal heart. The severity of the prognosis justifies screening tests. The genetic origin of the disease has been confirmed and at least 5 loci and 4 genes have been identified, giving a perfect illustration of adrenergic ventricular rhythm disorders. Beta-blockers are used as first line treatment in symptomatic patients.All drugs favoring QT interval lengthening are contraindicated in all subjects with a genetic anomaly. All members of the direct family must have a Holter recording and genotype in order to identify mutation carriers or asymptomatic patients.

The genetics of the long QT syndrome are now better understood. However, there is much heterogeneity as three different genes have already been identified affecting the function of sodium and potassium channels. The aim of these recommendations is to draw up a list of drugs which are contraindicated or not recommended in patients with congenital long QT syndromes. The conraindicated drugs are those with which torsades de pointe have already been described. Drugs not recommended are substances which are not electrohysiologically neutral and for which, in view of their modes of action, their metabolism or belonging to a particular therapeutic class, make them very difficult to use in those patients. It is therefore better not to prescribe them whenever possible in this condition. These substances belong mainly to cardiovascular (especially antiarrhythmic), psychotropic, anti-infectious and antiallergic groups of drugs.

Cisapride is frequently used in the newborn and infant for treatment of gastroesophageal reflux. Twisting-spikes have been reported in adults due to overdosage or therapeutic interaction. We report seven cases of QT prolongation in infants treated with cisapride.Seven children (one full-term, two mature preterms, four preterm babies), aged (mean, range) 41.8 +/- 21 days (14-79) weighing 2.1 +/- 1.1 kg (1.2-4), free from any cardiac abnormality, except one patent ductus arteriosus, have been studied by ECG and Holter monitoring. They received cisapride at a mean dose of 1.31 +/- 0.2 mg/kg/d (between 1 and 1.7 mg/kg/d).The corrected QT (QTc: N450 ms) was increased to 486 ms (450-540) with a notched T-wave pattern. No arrhythmia was detected. In five cases, cisapride was stopped and changed to metoclopramide. Cisapride dosage was reduced to 0.8 mg/kg/d in the two others. No other therapeutic modification was done. A control ECG performed 48 hours after therapeutic changes showed a QTc shortening of 74 +/- 18 ms (45-90) and the disappearance of the notches independent of any heart rate changes, leading to normal QTc values: 413 +/- 21 ms (390-440).High cisapride dosage in preterm, newborns and infants seems to favor QT prolongation which is reversible when dosage is reduced or drug is stopped. The use of cisapride in combination with other drugs known to increase QT should be done with extreme caution.

Extensively described since Gallvardin's reports, the electrical features of salves of ventricular tachycardia in an apparently healthy heart are now well known. The usual benign nature of this arrhythmia is acknowledged, seldom contradicted by isolated clinical cases. Although chronicity is the rule in young adults, there have been a few publications concerning the natural history of these tachycardias in the paediatric age group. The authors report three cases of episodic sustained ventricular tachycardia in older children, presenting at an average of 7 years of age (range 5 to 9 years) and followed up for an average of 7 years (range: 5.5 to 9 years). These three children were treated for an average of 4.5 years (range: 3 to 5.5 years). All treatment was finally withdrawn when stable permanent sinus rhythm without ventricular extrasystoles was restored and confirmed over an average period of 2 years (range 10 months to 3.5 years), an average of 4 (range 3 to 7) successive normal Holter recordings at several months' interval. The outcome in children to spontaneous regression after several years would seem to make radiofrequency ablation more dangerous than useful given the benign nature of the arrhythmia and its good response to pharmacological intervention.

To assess the cardiac and extracardiac safety and efficacy of flecainide versus propafenone in patients suffering from episodes of paroxysmal atrial fibrillation (AF) or atrial flutter, 97 patients were enrolled in a randomized, open-label, long-term, parallel, comparative multicenter study. The diagnosis of paroxysmal AF or atrial flutter had to be fully documented prior to inclusion in the study. Of the 97 patients enrolled in the study, 48 patients (25 men, 23 women, mean age 62.4 +/- 12.3 years) received flecainide; 49 patients (26 men, 23 women, mean age 63.6 +/- 12.2 years) received propafenone. The initial dose of flecainide was 50 mg twice daily, and this could be increased in steps of 50 mg twice daily every 4 days to a maximum of 300 mg/day. The initial dose of propafenone was 300 mg twice daily and this could be increased in steps of 300 mg every 4 days to a maximum of 1200 mg/day. At each visit, medical events, vital sign measurements (blood pressure, pulse rate), concomitant medications, adverse experiences, and study drug dosage changes were evaluated. Routine clinical laboratory tests were evaluated at the month 6 visit, and a 24-hr Holter recording was obtained at the month 1 visit. Almost half (45) of the patients were discontinued from the study before completing 1 year of therapy. The probability of successful treatment versus time--i.e., the proportion of patients who remained on therapy over the course of 1 year therapy--was 0.619 for the flecainide group and 0.469 for the propafenone group (p = 0.079; difference not significant). The difference is largely attributed to the higher proportion of patients in the propafenone group (9) than in the flecainide group (2) who experienced side effects important enough to stop the treatment. (The incidence of side effects was not statistically different between treatment groups, although it was higher in the propafenone group.) The proportion of patients who discontinued treatment due to inadequate response was similar in the 2 groups: 11 patients (22.9%) in the flecainide group and 12 patients (24.4%) in the propafenone group withdrew from the study, primarily because of an inadequate response, i.e., they experienced an increase in duration, frequency, and severity of attacks of AF or atrial flutter. Neurologic signs, central and peripheral, were mostly encountered in the flecainide group (8.5%), and, gastrointestinal effects were more often reported in the propafenone group (16.7%). In paroxysmal AF and paroxysmal atrial flutter, flecainide and propafenone are equally effective. However, in this study the probability of a patient's staying on flecainide after 1 year had a tendency to be higher than the probability of staying on propafenone, due to a greater proportion of secondary effects with propafenone.