Exercise testing in children with Wolff-Parkinson-White syndrome: what is its value?

This study was conducted to evaluate the accuracy of exercise testing for predicting accessory pathway characteristics in children with Wolff-Parkinson-White (WPW) syndrome. The study enrolled 37 children with WPW syndrome and candidates for invasive electrophysiologic study (EPS). Exercise testing was performed for all the study participants before the invasive study. Data from the invasive EPS were compared with findings from the exercise testing. The sudden disappearance of the delta (Δ) wave was seen in 10 cases (27 %). No significant correlation was found between the Δ wave disappearance and the antegrade effective refractory period of the accessory pathway (AERP-AP) or the shortest pre-excited RR interval (SPERRI). The sensitivity, specificity, and positive and negative predictive values of Δ wave disappearance, based on AERP-AP as gold standard, were respectively 29.4, 80, 71.4, and 40 %. The corresponding values with SPERRI as the gold standard were respectively 23.8, 71.4, 71.4 and 23.8 %. Exercise testing has a medium to low rate of accuracy in detecting low-risk WPW syndrome patients in the pediatric age group.

Hypertrophic cardiomyopathy and planned in vitro fertilization. Genetic testing and clinical evaluation.

Hypertrophic cardiomyopathy (HCM) is often transmitted to the offspring of affected individuals. This case report describes the role of genetic screening in a 39-year-old woman with a family history of sudden cardiac death. The patient wished to become pregnant and was seeking medical consultation. In addition to electro- and echocardiograms, genomic DNA was isolated and direct sequencing was employed to screen the patient for some of the most common genes that cause HCM. A pathogenic heterozygous mutation c.700 g > a p.Arg186Gln in TNNI3 was identified, which was not found in 200 normal control chromosomes. Mutation-specific genetic testing was also performed in four family members, and the same mutation was absent. Genetic screening appears cost effective in familiar members with a known mutation, provides important information about the affected individual, and can facilitate the future management of family members and offspring.

Extracardiac minimal invasive implantation of cardioverter defibrillator in young children.

Implantable cardioverter defibrillator (ICD) placement in young children remains a challenge due to device-patient size mismatch and the important choice between an endovenous or an epicardial approach for lead implantation. We treated three children, with respectively Long QT-syndrome, Brugada syndrome and Brugada syndrome with sick sinus syndrome, ranging from 9 months to 7 years with a subxyphoidal ICD and extracardiac lead implantation by minimally invasive techniques. In all cases the thresholds were excellent. The devices could be properly placed in the preperitoneal space without discomfort to the patients. The clinical course was uneventful and results were excellent.

Brugada syndrome: the prognostic dilemma and value of sincope.

Since its first description in 1992 as a new clinical entity, the Brugada syndrome has stimulated great interest among physicians and basic scientists. In 2002 and 2005, two consensus conferences have respectively defined the diagnostic criteria for the syndrome. Currently the diagnosis of Brugada syndrome is based on a combination of clinical events (syncope and/or sudden cardiac death due to malignant ventricular arrhythmias) and electrocardiographic features (pathognomonic ST-segment elevation morphology). In the last years, many advances have been done in the knowledge about the genetic basis, the cellular mechanisms responsible for the typical electrocardiography features, susceptibility to ventricular arrhythmias and risk stratification. The implantable cardioverter defibrillator remains the only therapeutic option of proven efficacy for primary and secondary prophylaxis of sudden cardiac death. Identification of high risk subjects is one of the major goals in clinical decision-making. Syncope is ubiquitously recognized as a bad prognostic marker in Brugada syndrome. However, young individuals with this disease may suffer from vaso-vagal instead of arrhythmic syncope. The prognostic significance of syncope in patients with Brugada syndrome is discussed in this review.

The Brugada syndrome: update 2006.

Over the last 14 years - since the Brugada syndrome was first recognized as a distinct clinical/electrocardiographical entity - a considerable number of papers have been published on its various aspects. It has been defined as the combination of a typical ST-segment elevation in the right precordial leads and a predisposition for malignant ventricular arrhythmias occurring in the absence of structural heart disease. From the outset, controversy arose about the diagnostic criteria to be applied. This issue has been clarified since the announcement of a first (2002) and second (2005) consensus report. Our review will discuss the clinical characteristics and different possible pathophysiological mechanisms underlying the specific ECG-abnormalities and susceptibility for malignant arrhythmias. Nowadays, the main issue of discussion revolves essentially around its prognostic features, especially in asymptomatic patients. This review will compare the results of different follow-up studies and yields a possible explanation for the differences in event rates and in the identification of useful sudden-death predictors. Finally, the most recent data concerning new diagnostic techniques, gene identification and future therapeutic options will also be discussed.

Brugada syndrome: a decade of progress.

The Brugada syndrome has gained wide recognition throughout the world and today is believed to be responsible for 4% to 12% of all sudden deaths and approximately 20% of deaths in patients with structurally normal hearts. The incidence of the disease is on the order of 5 per 10 000 inhabitants and, apart from accidents, is the leading cause of death of men under the age of 50 in regions of the world where the inherited syndrome is endemic. This minireview briefly summarizes the progress made over the past decade in our understanding of the clinical, genetic, cellular, ionic, and molecular aspects of this disease.

Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent.

The Brugada syndrome is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-segment elevation in V1 through V3 and a rapid polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation. Our group recently linked the disease to mutations in SCN5A, the gene encoding for the alpha subunit of the cardiac sodium channel. When heterologously expressed in frog oocytes, electrophysiological data recorded from the Thr1620Met missense mutant failed to adequately explain the electrocardiographic phenotype. Therefore, we sought to further characterize the electrophysiology of this mutant. We hypothesized that at more physiological temperatures, the missense mutation may change the gating of the sodium channel such that the net outward current is dramatically augmented during the early phases of the right ventricular action potential. In the present study, we test this hypothesis by expressing Thr1620Met in a mammalian cell line, using the patch-clamp technique to study the currents at 32 degrees C. Our results indicate that Thr1620Met current decay kinetics are faster when compared with the wild type at 32 degrees C. Recovery from inactivation was slower for Thr1620Met at 32 degrees C, and steady-state activation was significantly shifted. Our findings explain the features of the ECG of Brugada patients, illustrate for the first time a cardiac sodium channel mutation of which the arrhythmogenicity is revealed only at temperatures approaching the physiological range, and suggest that some patients may be more at risk during febrile states.

Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts.

BACKGROUND: A mutation in the cardiac sodium channel gene (SCN5A) has been described in patients with the syndrome of right bundle branch block, ST-segment elevation in leads V1 to V3, and sudden death (Brugada syndrome). These electrocardiographic manifestations are transient in many patients with the syndrome. The present study examined arrhythmic risk in patients with overt and concealed forms of the disease and the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk. METHODS AND RESULTS: The effect of intravenous ajmaline (1 mg/kg), procainamide (10 mg/kg), or flecainide (2 mg/kg) on the ECG was studied in 34 patients with the syndrome and transient normalization of the ECG (group A), 11 members of 3 families in whom a SCN5A mutation was associated with the syndrome and 8 members in whom it was not (group B), and 53 control subjects (group C). Ajmaline, procainamide, or flecainide administration resulted in ST-segment elevation and right bundle branch block in all patients in group A and in all 11 patients with the mutation in group B. A similar pattern could not be elicited in the 8 patients in group B who lacked the mutation or in any person in group C. The follow-up period (37+/-33 months) revealed no differences in the incidence of arrhythmia between the 34 patients in whom the phenotypic manifestation of the syndrome was transient and the 24 patients in whom it was persistent (log-rank, 0.639). CONCLUSIONS: The data demonstrated a similar incidence of potentially lethal arrhythmias in patients displaying transient versus persistent ST-segment elevation and right bundle branch block, as well as the effectiveness of sodium channel blockers to unmask the syndrome and, thus, identify patients at risk.

Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report.

OBJECTIVES: The objectives of this study were to present data on eight patients with recurrent episodes of aborted sudden death unexplainable by currently known diseases whose common clinical and electrocardiographic (ECG) features define them as having a distinct syndrome different from idiopathic ventricular fibrillation. BACKGROUND: Among patients with ventricular arrhythmias who have no structural heart disease, several subgroups have been defined. The present patients constitute an additional subgroup with these findings. METHODS: The study group consisted of eight patients, six male and two female, with recurrent episodes of aborted sudden death. Clinical and laboratory data and results of electrocardiography, electrophysiology, echocardiography, angiography, histologic study and exercise testing were available in most cases. RESULTS: The ECG during sinus rhythm showed right bundle branch block, normal QT interval and persistent ST segment elevation in precordial leads V1 to V2-V3 not explainable by electrolyte disturbances, ischemia or structural heart disease. No histologic abnormalities were found in the four patients in whom ventricular biopsies were performed. The arrhythmia leading to (aborted) sudden death was a rapid polymorphic ventricular tachycardia initiating after a short coupled ventricular extrasystole. A similar arrhythmia was initiated by two to three ventricular extrastimuli in four of the seven patients studied by programmed electrical stimulation. Four patients had a prolonged HV interval during sinus rhythm. One patient receiving amiodarone died suddenly during implantation of a demand ventricular pacemaker. The arrhythmia of two patients was controlled with a beta-adrenergic blocking agent. Four patients received an implantable defibrillator that was subsequently used by one of them, and all four are alive. The remaining patient received a demand ventricular pacemaker and his arrhythmia is controlled with amiodarone and diphenylhydantoin. CONCLUSIONS: Common clinical and ECG features define a distinct syndrome in this group of patients. Its causes remain unknown.

Treatment of cardiac arrhythmias: when, how and where?

Despite major advances in the understanding of mechanisms, better diagnostic methods and a wide array of new modes of therapy, management of cardiac arrhythmias continues to be a challenge. Because of possible deleterious effects of antiarrhythmic therapy, the decision about when and how to treat should be weighed carefully with emphasis on symptoms and the prognostic significance of the arrhythmia. When possible, the high risk patient should be referred to a center where expertise and diagnostic and therapeutic possibilities allow optimal treatment.

Transient entrainment and interruption of atrioventricular node tachycardia.

The possibility of transiently entraining and interrupting the common type of atrioventricular (AV) node tachycardia (anterograde slow, retrograde fast AV node pathway) was studied using atrial and ventricular pacing in 18 patients with paroxysmal AV node tachycardia. Transient entrainment occurred in all patients. During atrial pacing, localized block in the AV node for one beat followed by anterograde conduction over the fast pathway was observed in three patients. During ventricular pacing, localized block for one beat followed by retrograde conduction over the slow pathway was not observed in any patient. Neither atrial nor ventricular fusion beats were observed during entrainment. These observations indicate in a way not previously shown that reentry involving two functionally dissociated pathways in the AV node is the underlying mechanism of paroxysmal AV node tachycardia. The inability to demonstrate atrial or ventricular fusion beats during entrainment suggests a true intranodal location of the reentrant circuit. Finally, the ability to transiently entrain intranodal tachycardia demonstrates that this electrophysiologic phenomenon is not exclusively limited to macroreentrant circuits.

Observations on the antidromic type of circus movement tachycardia in the Wolff-Parkinson-White syndrome.

In the differential diagnosis of tachycardias showing a wide QRS complex and having a 1 to 1 relation between ventricular and atrial events, a supraventricular tachycardia with anterograde conduction over an accessory pathway and retrograde conduction by way of the specific conduction system must be considered. Five patients showing this type of circus movement tachycardia were studied by programmed electrical stimulation of the heart. Sudden changes in the tachycardia cycle length were observed in these patients that were based on changes in the VH interval. This finding suggested a change in the reentrant circuit with anterograde conduction over the accessory pathway but retrograde conduction sometimes occurring over the right bundle branch and at other times over one of the two divisions of the left bundle branch system. Characteristically, the tachycardia cycle length changed suddenly depending on the bundle branch used in retrograde direction. In one patient, an important difference was also observed between the anterograde effective refractory period of the accessory bypass (280 ms) and the shortest RR interval between preexcited QRS complexes during atrial fibrillation (measuring 190 ms). It is postulated that the short RR intervals during atrial fibrillation in the Wolff-Parkinson-White syndrome could result from bundle branch reentry after activation of the ventricles over the accessory pathway.

Multiple circus movement tachycardias with multiple accessory pathways.

A patient with the Wolff-Parkinson-White syndrome manifesting four types of tachycardia is described. The location and the participation during tachycardia of two different types of accessory atrioventricular pathways were documented during a programmed stimulation study. Unusual modes of initiation of tachycardias were observed, such as the initiation of an orthodromic circus movement tachycardia by an atrial premature beat that conducted in anterograde direction down the accessory pathway.

Value of the 12 lead electrocardiogram in diagnosing type and mechanism of a tachycardia: a survey among 22 cardiologists.

Information from programmed electrical stimulation of the heart has improved our ability to diagnose the site of origin and mechanism of a tachycardia from the 12 lead electrocardiogram. To test this hypothesis, the 12 lead electrocardiograms of a 12 year old girl with the Wolff-Parkinson-White syndrome showing four different types of tachycardia were sent for interpretation to 30 leading electrocardiologists , 22 of whom responded. A correct diagnosis of all four tachycardias was made by 13. Three or two of the tachycardias were correctly diagnosed by four and five cardiologists, respectively. The outcome of our study indicates that the pathway and mechanism of tachycardia can frequently be predicted from the 12 lead electrocardiogram alone.

Suppression of incessant supraventricular tachycardia by intravenous and oral encainide.

Although uncommon, incessant supraventricular tachycardia (the daily presence of supraventricular tachycardia for more than 50% of the day) is a major therapeutic problem. Using programmed electrical stimulation of the heart, long-term electrocardiographic monitoring and exercise testing, the effect of intravenous and oral encainide for termination and prevention of incessant supraventricular tachycardia was assessed in 11 patients (aged 25 to 58 years). All patients had received 3 to 12 drugs (mean 6) without control of their arrhythmia. Eight patients suffered from incessant supraventricular tachycardia using an accessory pathway in retrograde direction (three with overt Wolff-Parkinson-White syndrome, one with a concealed accessory atrioventricular [AV] pathway of the fast type, three with a concealed accessory AV pathway of the slow type and one with a nodo-ventricular accessory pathway). Three patients had incessant atrial tachycardia, one of whom also had the Wolff-Parkinson-White syndrome. Intravenous encainide (1.5 mg/kg in 15 minutes) terminated incessant supraventricular tachycardia in seven of nine patients. In four of nine patients, supraventricular tachycardia could thereafter still be reinitiated by pacing. Oral encainide (100 to 325 mg/day, mean 180) completely suppressed the incessant supraventricular tachycardia in eight patients in a follow-up period of 5 to 20 months (mean 11). In two patients, episodes of tachycardia were markedly reduced with the administration of encainide in combination with sotalol (one patient) and amiodarone (one patient). Encainide failed to control incessant tachycardia in one patient. Mild central nervous system side effects developed in two patients, but both could continue taking oral encainide. Encainide proved to be a very useful agent to control incessant supraventricular tachycardia resistant to other antiarrhythmic agents.

Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction.

Programmed electrical stimulation of the heart was prospectively used in 160 patients with healed myocardial infarction to study the incidence and characteristics of ventricular arrhythmias induced. Thirty-five patients had neither documented nor suspected ventricular arrhythmias (Group A); 37 patients had documented nonsustained ventricular tachycardia (Group B); 31 patients had been resuscitated from ventricular fibrillation (Group C); and 57 patients had documented sustained monomorphic ventricular tachycardia (Group D). No electrophysiologic differences were found between patients in Group A and Group B, but patients in both groups differed significantly from patients in Group C and Group D. In the last two groups, sustained monomorphic ventricular tachycardia was more frequently induced, the cycle length of the induced ventricular tachycardia was slower and a lesser number of premature stimuli was required for induction. No differences were found in the incidence, rate or mode of induction of nonsustained monomorphic ventricular tachycardia, but nonsustained polymorphic ventricular tachycardia and ventricular fibrillation were more frequently induced in Groups A and B. It is concluded that the substrate for sustained ventricular arrhythmia is present in at least 42% of patients after myocardial infarction. The electrophysiologic characteristics of the substrate for ventricular tachycardia seem to be the major determinant of the clinical occurrence of sustained ventricular arrhythmia. Changes in the electrophysiologic properties of the substrate of ventricular tachycardia, either spontaneously with time or induced by ischemia or antiarrhythmic drugs, can contribute to the clinical occurrence of sustained ventricular arrhythmias in patients with an old myocardial infarction.