Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.

BACKGROUND: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited. OBJECTIVES: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence. METHODS: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31). RESULTS: Patients' median age at time of first AE was 14 years, with a majority of males (74%), Caucasians (70%), and probands (79%) who presented as aborted cardiac arrest (84%). A significant proportion of patients (28%) exhibited fever-related AE. Family history of sudden cardiac death (SCD), prior syncope, spontaneous type 1 Brugada electrocardiogram (ECG), inducible ventricular fibrillation at electrophysiological study, and SCN5A mutations were present in 26%, 49%, 65%, 28%, and 58% of patients, respectively. The pediatric group differed from the adolescents, with a greater proportion of females, Caucasians, fever-related AEs, and spontaneous type-1 ECG. During follow-up, 68% of pediatric and 64% of adolescents had recurrent AE, with median time of 9.9 and 27.0 months, respectively. Approximately one-third of recurrent AEs occurred on quinidine therapy, and among the pediatric group, 60% of recurrent AEs were fever-related. Risk factors for recurrent AE included sinus node dysfunction, atrial arrhythmias, intraventricular conduction delay, or large S-wave on ECG lead I in the pediatric group and the presence of SCN5A mutation among adolescents. CONCLUSIONS: Young BrS patients with AE represent a very arrhythmogenic group. Current management after first arrhythmia episode is associated with high recurrence rate. Alternative therapies, besides defibrillator implantation, should be considered.

Long-term follow-up of asymptomatic Brugada patients with inducible ventricular fibrillation under hydroquinidine.

AIMS: To evaluate the long-term efficacy and safety of an electrophysiologically guided therapy, based on a strategy of treatment using hydroquinidine (HQ) among asymptomatic Brugada patients with inducible ventricular fibrillation (VF). METHODS AND RESULTS: In two French reference centres, consecutive asymptomatic type 1 Brugada patients with inducible VF were treated with HQ (600 mg/day, targeting a therapeutic range between 3 and 6 µmol/L) and enroled in a specific follow-up (mean 6.6 ± 3 years), including a second programmed ventricular stimulation (PVS) under HQ. An implantable cardioverter defibrillator (ICD) was eventually implanted in patients inducible under HQ, or during follow-up in case of HQ intolerance, as well as occurrence of arrhythmic events. From a total of 397 Brugada patients, 44 were enroled (47 ± 10 years, 95% male). Of these, 34 (77%) were no more inducible (Group PVS-), and were maintained under HQ alone during a mean follow-up of 6.2 ± 3 years. In this group, an ICD was eventually implanted in four patients (12%), with occurrence of appropriate ICD therapies in one. Among the 10 other patients (22%), who remained inducible and received ICD (Group PVS+), none of them received appropriate therapy during a mean follow-up of 7.7 ± 2 years. The overall annual rate of arrhythmic events was 1.04% (95% confidence interval 0.00-2.21), without any significant difference according to the result of PVS under HQ. One-third of patients experienced device-related complications. CONCLUSION: Our long-term follow-up results emphasize that the rate of arrhythmic events among asymptomatic Brugada patients with inducible VF remains low over time. Our results also suggest that residual inducibility under HQ is of limited value to predict events during follow-up.

Ventricular repolarization restitution properties in patients exhibiting type 1 Brugada electrocardiogram with and without inducible ventricular fibrillation.

OBJECTIVES: This study aimed to elucidate the contribution of the repolarization restitution property to the sustained ventricular fibrillation (VF) in Brugada syndrome. BACKGROUND: Although phase 2 re-entry develops as the trigger of VF, the other precipitating factors have remained unclear. METHODS: Twenty-one patients with a type 1 Brugada electrocardiogram underwent programmed electrical stimulation. Before the VF induction, single extrastimuli were delivered at 3 basic drive cycle lengths (BCLs) (400 ms, 600 ms, and 750 ms) from the right ventricular apex (RVA) and outflow tract (RVOT), and the activation recovery interval (ARI) was measured at 5-mm vicinity of the pacing site. The maximum ARI restitution slope was determined using the overlapping least-squares linear segments. RESULTS: We found that VF was inducible in 10 patients. A repeated-measure analysis of variance revealed that the slope in the RVA was steeper in patients with inducible VF than in those without but that in the RVOT was similar. The slope was steeper at longer BCLs and also steeper in the RVA than RVOT at BCLs of 600 and 750 ms. In patients with inducible VF, the percentage of patients exhibiting a slope >1 was 0%, 20%, and 75% in the RVA and 0%, 0%, and 14% in the RVOT at BCLs of 400 ms, 600 ms, and 750 ms, respectively. No patients without inducible VF had a slope >1. CONCLUSIONS: These results suggest the repolarization restitution property is a contributing factor to the propensity for VF in Brugada syndrome and, regarding this property, the RVA plays more important role than the RVOT.

Clinical implications of "pure" Hisian pacing in addition to para-Hisian pacing for the diagnosis of supraventricular tachycardia.

BACKGROUND: Para-Hisian pacing is an effective method of differentiating between pathways for retrograde conduction over the accessory pathway (AP) and over the atrioventricular node (AVN). When performing para-Hisian pacing, the pacing spike sometimes captures only the His bundle, which we named "pure" Hisian pacing (Hc). OBJECTIVE: We evaluated the significance of pure Hisian pacing for predicting the pathways of ventriculoatrial conduction. METHODS: In 62 patients with supraventricular tachycardia, both para-Hisian and pure Hisian pacing were carried out during the sinus rhythm, resulting in three different types of electrocardiographic complexes with wide (local ventricular myocardial capture), slightly narrow (both local myocardial and His bundle capture), and very narrow QRS widths (Hc). A change of atrial activation sequence as demonstrated by these pacing modes indicated the presence of multiple retrograde pathways. The diagnosis of retrograde pathways by para-Hisian pacing with or without Hc was evaluated. RESULTS: In 22 patients with AVN reentrant tachycardia, para-Hisian pacing alone was able to correctly predict ventriculo-atrial conduction exclusively through the AVN without requiring findings from Hc. In 40 AP patients, para-Hisian pacing showed a pattern of retrograde conduction through the AVN in six, through both the AVN and AP in 10, and through an AP in 24 patients. Four of these 24 patients were diagnosed as having multiple pathways (AP+AVN or dual APs) by the addition of Hc. CONCLUSION: Pure Hisian pacing can help disclose another pathway for retrograde conduction in AP patients, which is unpredicted by ordinary para-Hisian pacing.

Decreased nocturnal standard deviation of averaged NN intervals. An independent marker to identify patients at risk in the Brugada Syndrome.

AIMS: Risk-stratification of asymptomatic Brugada Syndrome (BS) patients remains a key-issue. A typical spontaneous BS-ECG pattern and ventricular tachycardia (VT)/ventricular fibrillation (VF) inducibility are two recognized risk markers. The aim of the study was to identify additional risk markers in asymptomatic BS. METHODS AND RESULTS: We have compared Holter recordings in symptomatic and in asymptomatic patients with BS. Heart rate variability (HRV), QT-interval rate-dependence and ST-segment elevation (ST-SE) were analysed. The study population included 47 BS patients (M=36, mean age=45+/-13 years) with a malignant ventricular arrhythmia in 11 cases, an unexplained syncope in 10 cases and no symptoms in the remaining 26 cases. A typical spontaneous BS-ECG was present in 21 cases and a drug-induced BS-ECG in 26 cases. A downward trend of the time domain variables of HRV was observed. During the nocturnal period, standard deviation (SD) of the 5min averaged NN intervals (SDANN) (46+/-13 vs 57+/-18ms, P=0.02) and ultra low frequency component (3287+/-2312 vs 5030+/-3270 ms(2), P=0.04) were significantly lower in symptomatic versus asymptomatic patients. In contrast, no difference was found in QT-interval rate dependence and in ST-SE. At multivariate logistic regression, VT/VF inducibility, typical spontaneous BS-ECG and a decreased nocturnal SDANN were associated with arrhythmic events (P=0.003). CONCLUSIONS: A decreased nocturnal SDANN was an independent marker of arrhythmic events in these BS patients.

Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes.

BACKGROUND: The long-QT and Brugada syndromes are important substrates of malignant ventricular arrhythmia. The feasibility of mapping and ablation of ventricular arrhythmias in these conditions has not been reported. METHODS AND RESULTS: Seven patients (4 men; age, 38+/-7 years; 4 with long-QT and 3 with Brugada syndrome) with episodes of ventricular fibrillation or polymorphic ventricular tachycardia and frequent isolated or repetitive premature beats were studied. These premature beats were observed to trigger ventricular arrhythmias and were localized by mapping the earliest endocardial activity. In 4 patients, premature beats originated from the peripheral right (1 Brugada) or left (3 long-QT) Purkinje conducting system and were associated with variable Purkinje-to-muscle conduction times (30 to 110 ms). In the remaining 3 patients, premature beats originated from the right ventricular outflow tract, being 25 to 40 ms ahead of the QRS. The accuracy of mapping was confirmed by acute elimination of premature beats after 12+/-6 minutes of radiofrequency applications. During a follow-up of 17+/-17 months using ambulatory monitoring and defibrillator memory interrogation, no patients had recurrence of symptomatic ventricular arrhythmia but 1 had persistent premature beats. CONCLUSIONS: Triggers from the Purkinje arborization or the right ventricular outflow tract have a crucial role in initiating ventricular fibrillation associated with the long-QT and Brugada syndromes. These can be eliminated by focal radiofrequency ablation.

Diagnosis and management of out-of-hospital cardiac arrest secondary to coronary artery spasm.

OBJECTIVE: The clinical features of coronary artery spasm as a cause of cardiac arrest were determined in a prospective study on out-of-hospital cardiac arrest (OHCA). METHODS: Coronary angiography was performed at admission in 300 consecutive patients with no obvious non-cardiac cause of OHCA. In survivors with no or minimal coronary artery stenosis, a second angiography with provocation test and electrophysiological testing were performed at 1 month. RESULTS: Spasm was demonstrated in ten patients. Diagnosis was based upon (1) spontaneous spasm on the admission angiogram (3 patients), (2) transient significative ST-segment elevation at follow-up in patients with no or non-significant coronary artery lesions (4 patients) and (3) spasm during the 1 month provocation test (3 patients). Six patients survived at 1 month; spasm occurred during a new provocation test in five despite treatment with high dosage calcium channel blockers leading to coronary stenting in two, an internal cardiovertor defibrillator in one, and increased drug therapy with prolonged hospitalization in the remainder. At a mean follow-up of 55+/-27 months, no recurrent cardiac arrest occurred. CONCLUSION: Systematic coronary angiograms and provocation tests in survivors of OHCA allow prompt diagnosis of coronary artery spasm. Residual spasm despite treatment with calcium channel blockers is frequent. Therapy should therefore be guided by repetitive provocation tests, and seems to avoid recurrence of cardiac arrest.