Asymptomatic Brugada Syndrome Patients Research Articles

The Role of Electrophysiological Study in the Risk Stratification of Brugada Syndrome.

Brugada syndrome (BrS) is a complex arrhythmogenic disease associated with an increased risk of sudden cardiac death (SCD). The role of electrophysiological study (EPS) for risk stratification purposes of asymptomatic BrS patients remains still controversial. This study aims to summarize the existing data about the role of electrophysiological study for arrhythmic risk stratification of BrS patients without a prior history of aborted SCD or fatal arrhythmic event. Two independent investigators (G.B. and G.T.) performed a systematic search in the MedLine database and Cochrane library from their inception until April 2022 without any limitations. The reference lists of the relevant research studies as well as the relevant review studies and meta-analyses were manually searched. Nineteen studies were included in the final analysis. The included studies enrolled 6218 BrS patients (mean age: 46.9 years old, males: 76%) while 4265 (68.6%) patients underwent an EPS. The quantitative synthesis showed that a positive EPS study was significantly associated with arrhythmic events in BrS patients (RR, 1.74 [1.23-2.45]; P = 0.002; I2 = 63%]. By including the studies that provided data on the association of EPS with arrhythmic events during follow-up in patients without a prior history of aborted SCD or fatal arrhythmic event, the association between positive EPS study and future arrhythmic events remained significant (RR, 1.60 [1.08-2.36]; P = 0.02; I2 = 19%). In conclusion, EPS is a useful invasive tool for the risk stratification of BrS patients and can be used to identify the population of BrS patients who may be candidates for primary prevention of SCD with implantable cardioverter-defibrillator (ICD) implantation.

Abstract 11307: Longer Outflow Tract Conduction Time by Magnetocardiography as a Novel Non-Invasive Maker for Predicting Lethal Events in Patients With Brugada Syndrome Without Ventricular Fibrillation

Introduction: Many of the Brugada syndrome (BrS) patients have no symptom or only syncope without ventricular fibrillation (VF)/sudden cardiac death (SCD), thus to whom we should recommend implantable cardioverter defibrillator (ICD) for primary prevention of SCD is still the biggest concern in the BrS. Here we investigated whether a high spatial resolution magnetocardiography (MCG) could predict lethal events of the BrS without history of VF/SCD. Methods: This study retrospectively enrolled 157 BrS patients without VF or cardiopulmonary arrest (CPA) (150 male, 42±13 years old, 118 spontaneous and 39 drug-induced type-1 ECG). Outflow tract conduction time (OT-CT) from 2-D current map of MCG was measured in all patients as well as the standard 12-lead ECG and signal-averaged ECG (SAECG). Programmed electrical stimulation (PES) for VF induction was performed in 47 patients. Results: Patients with spontaneous type-1 ECG had longer OT-CT compared with type-2 BrS patients. Na channel blocker, pilsicainide (25-50mg) unmasked type-1 ECG as well as increased OT-CT (54±18 to 127±62 ms; p<0.05), whereas additional isoproterenol (1ug/kg/min) reversed the pilsicainide-induced delayed OT-CT, thus normalized the ST elevation of ECG. During follow-up (mean 72 [6-147] months), 10 (6%) patients suffered VF/CPA, and those had a higher incidence of previous syncope (50% vs. 14.4%, p=0.01) and longer baseline OT-CT (83±31ms vs. 55±24ms, p=0.01) compared with event-free patients. Receiver operating curve (ROC) revealed OT-CT=65ms was a cut-off value of VF/CPA (AUC=0.78), whereas, spontaneous type-1 ECG, late potential of SAECG, family history, and VF inducibility by PES were not associated with VF/CPA events during follow-up. Multivariate Cox proportional analysis revealed that previous syncope (HR=1.70, 95%CI:1.01-3.05, p=0.04) and OT-CT≥65ms (HR=1.72, 95%CI=1.16-2.62) were the independent predictor for lethal events in the BrS without VF/CPA. Among asymptomatic BrS patients (n=131), OT-CT≥65ms was also an independent predictor for VF/CPA (HR=1.69, 95%CI=1.04-2.79, p=0.03). Conclusion: Longer OT-CT in the MCG may noninvasively demonstrate substrate of VF in BrS and stratify the risk of lethal events in patients with BrS without history of VF or CPA.

Brugada Syndrome as a Major Cause of Sudden Cardiac Death in Asians.

Brugada syndrome (BrS) is one of the main inherited arrhythmia syndromes causing ventricular fibrillation (VF) and sudden cardiac death in young to middle-aged men, especially in Asians. The diagnosis of BrS is based on spontaneous or drug-provoked type 1 Brugada electrocardiogram. The current reliable therapy for BrS patients with VF history is the implantation of an implantable cardioverter-defibrillator. As for BrS patients without VF history, how asymptomatic BrSpatients should effectively be treated is still uncertain because risk stratification of the BrS is still inadequate. Variousparameters and combinations of several parameters have been reported for risk stratification of BrS. The SCN5A gene is believed to be the only gene that is responsible for BrS, and it has been reported to be useful for risk stratification. This review focuses on risk stratification of BrS patients, and focuses specifically on BrS patients of Asian descent.

Multivariate ensemble classification for the prediction of symptoms in patients with Brugada syndrome.

Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients. Graphical abstract Pipeline for feature selection and predictive modeling of symptoms in Brugada syndrome.

Risk stratification in asymptomatic patients with Brugada syndrome: Utility of multiple risk factor combination rather than programmed electrical stimulation.

The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. Asymptomatic BrS patients generally have a better prognosis than those with symptoms. The purpose of this study was to evaluate the value of nonaggressive PES with up to two extra stimuli and predict clinical factors for risk stratification in asymptomatic BrS patients. The study enrolled 193 consecutive asymptomatic BrS patients with type 1 ECG (mean age: 50 ± 13 years, 180 males) who underwent PES using a nonaggressive uniform protocol. Cardiac events (CEs: sudden cardiac death or ventricular tachyarrhythmia) during the follow-up period were examined. During a mean follow-up of 101 ± 48 months, seven asymptomatic patients (3.6%) had a CE. The incidence of CEs was not different between patients with and without inducible ventricular tachyarrhythmia by PES (p = .51). The clinical significance of risk factor combinations, including spontaneous type 1 ECG, family history of sudden cardiac death, QRS duration in lead V2 , and presence of J wave, was evaluated. Using the Kaplan-Meier method according to the number of risk factors, the prevalence of CE in patients with three or four risk factors was determined to be significantly higher than in those with one risk factor (p = .02 and p = .004, respectively). The present study suggests that inducibility of ventricular tachyarrhythmia does not predict future CEs in asymptomatic BrS patients. Combination analysis of the other four clinical risk parameters may be effective for risk assessment.

Dynamic changes in ventricular depolarization during exercise in patients with Brugada syndrome.

Brugada syndrome (BS) is a genetic pathological condition associated with a high risk for sudden cardiac death (SCD). Ventricular depolarization disorders have been suggested as a potential electrophysiological mechanism associated with high SCD risk on patients with BS. This paper aims to characterize the dynamic changes of ventricular depolarization observed during physical exercise in symptomatic and asymptomatic BS patients. To this end, cardiac ventricular depolarization features were automatically extracted from 12-lead ECG recordings acquired during standardized exercise stress test in 110 BS patients, of whom 25 were symptomatic. Conventional parameters were evaluated, including QRS duration, R and S wave amplitudes (, ), as well as QRS morphological features, such as up-stroke and down-stroke slopes of the R and S waves (, and ). The effects of physical exercise and recovery on the dynamics of these markers were assessed in both BS populations. Features showing significantly different dynamics between the studied groups were used alone and in combination with the clinical characteristics of the patients in a logistic regression analysis. Results show larger changes in the second half of the QRS complex through and measured in the right precordial leads for asymptomatic patients, especially during recovery, when the vagal tone is more pronounced. Multivariate analysis involving both types of features resulted in a reduced model of three relevant features ( in lead V2, Sex and heart rate recovery, HRR), which achieved a suitable discrimination performance between groups; sensitivity = 80% and specificity = 75% (AUC = 83%). However, after controlling the model for possible confounding factors, only one feature () remained meaningful. This adjusted model significantly improved the overall discrimination performance by up to: sensitivity = 84% and specificity = 100% (AUC = 94%). The study highlights the importance of physical exercise test to unmask differentiated behaviors between symptomatic and asymptomatic BS patients through depolarization dynamic analysis. This analysis together with the obtained model may help to identify asymptomatic patients at low or high risk of future cardiac events, but it should be confirmed by further prospective studies.

Model-based analysis of the autonomic response to head-up tilt testing in Brugada syndrome

The etiology of Brugada syndrome (BS) is complex and multifactorial, making risk stratification in this population a major challenge. Since changes in the autonomic modulation of these patients are commonly related to arrhythmic events, we analyze in this work whether the response to head-up tilt (HUT) testing on this population may provide useful, complementary information for risk stratification. In order to perform this analysis, a coupled physiological model integrating the cardiac electrical activity, the cardiovascular system and the baroreceptors reflex control of the autonomic function, in response to HUT is proposed. A sensitivity analysis was performed, based on a screening method, evidencing the influence of cardiovascular parameters on blood pressure and of baroreflex regulation on heart rate. The most sensitive parameters have been identified on a set of 20 subjects (8 controls and 12 BS patients), so as to assess subject-specific model parameters. According to the results, controls showed an increased sympathetic modulation after tilting, as well as a reduced left ventricular contractility was observed in symptomatic, with respect to asymptomatic BS patients. These results provide new insights regarding the autonomic mechanisms regulating the cardiovascular system in BS which might be used as a complementary source of information, along with classical electrophysiological parameters, for BS risk stratification.

Brugada Syndrome: The Role of Risk Stratification in Selecting Patients for Implantable Cardioverter-defibrillator Placement.

Brugada syndrome (BS) is an inherited cardiac ion channelopathy that is a rare, but treatable, cause of sudden cardiac death (SCD). There are many studies that explore the management of symptomatic BS, but few trials have been conducted regarding management of asymptomatic Brugada patients. Asymptomatic BS patients are shown to be at increased risk (0.5%-1.5%) for SCD compared to the general population and account for nearly 20% of deaths from SCD in patients with structurally normal hearts. Treatment for asymptomatic BS patients is often debated with the current guidelines allowing for management decisions to be made on a case-by-case basis. Therapies include either anti-arrhythmic medications, implantable cardioverter-defibrillator (ICD) placement, or no active treatment. This review intended to assess whether ICD placement benefits asymptomatic BS patients and what criteria may be useful in selecting patients for ICD placement. Results showed that ICD placement can reduce mortality in select asymptomatic patients. There were certain risk factors that increased the likelihood that an asymptomatic patient would experience SCD and thus benefit from an ICD. These factors include an electrocardiogram(ECG) demonstrating spontaneous type 1 Brugada Syndrome and inducibility of ventricular tachyarrhythmias during electrophysiological study. Other variables including gender, family history of SCD, and the presence of SCN5A mutation were not predictive of arrhythmic events. Moreover, many patients can suffer complications from ICDs that can affect the quality of life including inappropriate shocks, device malfunction, infection, mental health problems, and difficulties with replacements. Guidelines for quantifying the risk of SCD relative to the risks associated with ICD placement are still poorly defined. These complications and risk factors should be taken into consideration in the context of a patient-centered discussion regarding ICD placement in asymptomatic patients.

Heart rate differences between symptomatic and asymptomatic Brugada syndrome patients at night

Objective: Ventricular arrhythmias in Brugada syndrome (BS) mainly occur at rest, especially during nighttime, suggesting that parasympathetic activity at night may play an important role in the arrhythmogenesis of the disease. This study examined and compared the autonomic function of symptomatic and asymptomatic BS patients overnight. Approach: We analyzed various heart rate variability (HRV) and heart rate complexity (HRC) markers in a clinical series including 87 BS patients, where 23 were symptomatic. Main results: Statistically significant differences were found in markers MIRR, SDNN, SDANN, and SampEn, suggesting that symptomatic patients may be related to lower heart rate variability and complexity values, as well as to greater circadian fluctuations overnight. Significance: The results provide further evidence for the role of autonomic imbalance in the pathophysiology of BS, highlighting the relevance of nighttime analysis to the unmasking of significant ANS changes. Based on these outcomes, the role of HRV and HRC assessment at night could be a step forward towards the understanding of BS and the risk for the occurrence of symptoms in these patients, with a potential future impact on therapeutic strategies.

Prolonged Right Ventricular Ejection Delay in Brugada Syndrome Depends on the Type of SCN5A Variant - Electromechanical Coupling Through Tissue Velocity Imaging as a Bridge Between Genotyping and Phenotyping.

Patients with Brugada syndrome (BrS) and a history of syncope or sustained ventricular arrhythmia have longer right ventricular ejection delays (RVEDs) than asymptomatic BrS patients. Different types ofSCN5Avariants leading to different reductions in sodium current (INa) may have different effects on conduction delay, and consequently on electromechanical coupling (i.e., RVED). Thus, we investigated the genotype-phenotype relationship by measuring RVED to establish whether BrS patients carrying more severeSCN5Avariants leading to premature protein truncation (T) and presumably 100%INareduction have a longer RVED than patients carrying missense variants (M) with different degrees ofINareduction.Methods and Results:There were 34 BrS patients (mean [±SD] age 43.3±12.9 years; 52.9% male) carrying anSCN5Avariant and 66 non-carriers in this cross-sectional study. Patients carrying aSCN5Avariant were divided into T-carriers (n=13) and M-carriers (n=21). Using tissue velocity imaging, RVED and left ventricular ejection delay (LVED) were measured as the time from QRS onset to the onset of the systolic ejection wave at the end of the isovolumetric contraction. T-carriers had longer RVEDs than M-carriers (139.3±15.1 vs. 124.8±11.9 ms, respectively; P=0.008) and non-carriers (127.7±17.3 ms, P=0.027). There were no differences in LVED among groups. Using the simple, non-invasive echocardiographic parameter RVED revealed a more pronounced 'electromechanical' delay in BrS patients carrying T variants ofSCN5A.

Heart rate complexity analysis in Brugada syndrome during physical stress testing

Symptoms such as ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest, especially during sleep, suggesting that the autonomic nervous system (ANS) function may be relevant in the arrhythmogenesis of the disease. The aim of this work was to assess the ANS response captured by nonlinear heart rate variability (HRV) measures in 69 patients diagnosed with BS, who underwent a standardized physical stress test. Heart rate complexity (HRC) was evaluated by the power-law scaling analysis (β slope) during rest, exercise, recovery and rest post-recovery, in order to discriminate between symptomatic and asymptomatic BS patients. Symptomatic patients showed a significant reduction in HRC in comparison to asymptomatic subjects, after exertion (p = 0.015); during the whole recovery period (p = 0.023), and in particular within the passive recovery phase (p = 0.025), as well as during rest post-recovery (p = 0.022). Based on these results, symptoms could be associated with a lower ANS complexity during the stress test stages where parasympathetic activity is predominant. Therefore, the proposed HRV indicators could be of help in the risk stratification of asymptomatic patients.

Risk stratification of ventricular fibrillation in Brugada syndrome using noninvasive scoring methods

Risk stratification for ventricular fibrillation (VF) in patients with Brugada syndrome (BrS) remains controversial. The purpose of this study was to construct a novel prediction model for VF risk in BrS patients using noninvasive parameters. A total of 143 Japanese BrS patients with VF (n = 35) and without VF (n = 108) were retrospectively enrolled. We built a logistic regression model predicting VF occurrence and evaluated it by cross-validation. Frequencies of history of syncope and spontaneous type 1 ECG, r-J interval in V1, QRS duration in V6, and LAS40, Tpeak-Tend dispersion, and max T-wave alternans were significantly associated with VF occurrence in univariate analyses. The history of syncope, r-J interval in V1, QRS duration in V6, and Tpeak-Tend dispersion were identified as independent predictors by multivariate logistic regression analysis. The predictive model was constructed using all these parameters with good discrimination of VF occurrence (area under the curve 0.869 with 97.1% sensitivity and 65.7% specificity). The area under the curve based on leave-one-out cross-validation was 0.845, with 97.1% sensitivity and 63.0% specificity suggesting good performance of the model. Retrospective survival analysis revealed that the cumulative VF event rate was significantly higher in patients at high risk than in those with low risk using the log rank test (P = 2.97 × 10(-8)). Notably, no BrS patient below the cutoff value developed a subsequent VF event. This novel prediction method may effectively assesses VF risk in BrS patients, especially when determining implantable cardioverter-defibrillator placement for asymptomatic BrS patients.

Brugada syndrome: diagnosis, risk stratification, and management.

Asymptomatic patients with Brugada syndrome (BrS) have a small, but not trivial, risk of cardiac events. Their risk stratification and its impact on their management are controversial. The review focuses on the clinical aspects of BrS with special emphasis on the asymptomatic patient. Emerging data suggest that drug and fever-induced type I Brugada patterns are more common than previously appreciated. Although preliminary, these data may imply that asymptomatic patients with induced Brugada pattern are at an even lower risk than currently estimated.The latest data regarding induced ventricular arrhythmias during electrophysiological studies support its use as an indication for an implantable cardioverter defibrillator; however, this issue remains highly controversial.Several new risk markers, such as presence of the Brugada pattern in infero-lateral leads or the concomitant finding of an early repolarization pattern, have recently been proposed. Most asymptomatic BrS patients are at low risk of cardiac events. The presence of new risk markers in this population may prompt consideration of primary prevention measures; however, data supporting this approach are still limited.

Abstract 11509: QT Rate Dependence is Reduced in Brugada Syndrome Independent of Genotypic Status

Introduction: Sudden cardiac death in Brugada syndrome (BrS) is most frequent in rest or during sleep suggesting an influence of the autonomic nervous system. Some limited data indicate reduced QT rate dependence and loss of its diurnal variation in BrS. Hypothesis: We evaluated the hypothesis that QT rate dependence and its diurnal variation is reduced in BrS and assessed whether presence of an SCN5A mutation influences this relationship. Methods: In this retrospective single center study we included 4 different groups: patients demonstrating a spontaneous or ajmaline-induced type 1 ECG with (N=17) and without (N=19) SCN5A mutation, carriers of an SCN5A mutation without phenotypic evidence of BrS based on serial ECG’s and provocation with ajmaline (N=22) and finally genotype negative family members of SCN5A mutation carriers as controls (N=25). All patients underwent 24 hour holter recordings. QT/RR analysis of 24 hour, daytime (8AM-9PM) and nighttime (11PM-6AM) data was performed along with manual review. Results: Age and sex were comparable between groups, as was the use of a beta-blocker (9 in the total group). 24 hour QT/RR slope was reduced both in the SCN5A positive (0.141±0.045; p=0.04) and negative BrS group (0.141±0.047; p=0.03) as in the phenotype negative genotype positive group (0.128±0.046; p=0.001) compared to controls (0.183±0.054). Daytime QT rate dependence remained significantly reduced in the 3 pathological states, however nighttime QT rate dependence was not. In controls there was a trend towards a diurnal variation of QT rate dependence (QT/RR slope day 0.152±0.063; night 0.129±0.05; p=0.13), however this was not the case in any of the other groups. There was a clear trend towards lower values in 10 symptomatic BrS patients (0.118±0.045) compared to 26 asymptomatic BrS patients (0.15±0.043; p=0.06). Conclusions: In this large cohort of BrS patients, QT rate dependence was reduced during 24 hour and daytime periods without evidence of diurnal variation and independent of the presence of an SCN5A mutation. This attenuation of QT rate dependency further underscores the role of a pathological response to autonomic nervous system modulation in BrS arrhythmogenesis, irrespective of SCN5A genotypic status.

Asymptomatic Brugada Syndrome: Clinical Characterization and Long-Term Prognosis.

Among Brugada syndrome patients, asymptomatic individuals are considered to be at the lowest risk. Nevertheless, arrhythmic events and sudden cardiac death are not negligible. Literature focused on this specific group of patients is sparse. The purpose of this study is to investigate the clinical characteristics, management, and long-term prognosis of asymptomatic Brugada syndrome patients. Patients presenting with spontaneous or drug-induced Brugada type I ECG and no symptoms at our institution were considered eligible. A total of 363 consecutive patients (200 men, 55.1%; mean age, 40.9±17.2 years; 41 [11.3%] with spontaneous type I ECG) were included. Electrophysiological study was performed in 321 (88.4%) patients, and ventricular arrhythmias were induced in 32 (10%) patients. An implantable cardioverter defibrillator was implanted in 61 (16.8%) patients. After a mean follow-up time of 73.2±58.9 months, 9 arrhythmic events occurred, accounting for an annual incidence rate of 0.5%. Event-free survival was 99.0% at 1 year, 96.2% at 5 years, and 95.4% at 10 and 15 years. Univariate analysis identified as risk factors: electrophysiological study inducibility (hazard ratio, 11.4; P<0.01), spontaneous type I (hazard ratio, 4.0; P=0.04), and previous sinus node dysfunction (hazard ratio, 8.0; 95% confidence interval, 1.0-63.9; P=0.05). At the multivariate analysis, only inducibility remained significant (hazard ratio, 9.1; P<0.01). Arrhythmic events in asymptomatic Brugada syndrome patients are not insignificant. Ventricular arrhythmia inducibility, spontaneous type I ECG, and presence of sinus node dysfunction might be considered as risk factors and used to drive long-term management.

The Diagnosis, Risk Stratification, and Treatment of Brugada Syndrome.

Brugada syndrome (BrS) is among the more common familial arrhythmia syndromes, with an estimated prevalence of 1 to 5 per 10 000 persons. It is characterized by a right ventricular conduction delay, dynamic or persistent ST-segment elevations in the precordial leads V1-3 , and an elevated risk of syncope and sudden cardiac death in young adults without structural heart disease. This article is based on original and review articles on BrS that appeared in English from 2010 onward and were retrieved by a selective search in PubMed, with special attention to international consensus publications on inherited arrhythmogenic diseases. According to the new diagnostic criteria, the diagnosis of BrS requires typical ECG changes in only one precordial lead. This will likely increase sensitivity, but may also lead to an increase in asymptomatic patients. Established risk markers include sudden cardiac arrest and a spontaneous type 1 ECG with arrhythmic syncope. Patients with these findings benefit from the implantation of a cardioverter-defibrillator. There is no validated algorithm for risk stratification of asymptomatic patients. Because of the low prevalence of BrS, there have been no randomized controlled trials (RCTs) in this disease, and all recommendations are based on expert opinion. BrS is usually inherited in an autosomal dominant manner. Recently discovered gene polymorphisms modify the risk of BrS, challenging the conception of BrS as a monogenetic disease. Electro-anatomic mapping studies have revealed, for the first time, an arrhythmogenic substrate over the right ventricular outflow tract in BrS patients. BrS is one important differential diagnosis to consider in patients presenting with syncope or sudden cardiac arrest. The goal of current research is to achieve a deeper understanding of the genetic and electrophysiological changes underlying BrS. Further insights in these areas will probably enable better risk stratification of asymptomatic BrS patients in the future.

0439 : Incidence of inappropriate ICD shocks and other complications in asymptomatic versus symptomatic Brugada syndrome

Brugada syndrome (BrS) requires implantation of cardioverter- defibrillator (ICD) to prevent sudden cardiac death. However, the ICD indications in asymptomatic patients are remain conflicting. We compared the rate of ICD complications in asymptomatic versus symptomatic BrS patients. ICD interrogations were done every 3-6 months. Given the low prevalence of BrS in the general population, 10% of the risk a?for the bilateral statistical test significance was chosen. We studied 51 patients, 86.5% male; mean age 4711 years at diagnosis. At diagnosis, 18 patients (35%) were asymptomatic, 25 patients (49%) experienced syncope, and 8 patients (16%) had been resuscitated from ventricular fibrillation. During a mean follow-up of 78±months, none of asymptomatic patients experienced appropriate therapy, whereas 21.6% of symptomatic patients had =1 shocks. Overall complication rate was 27.4%. Inappropriate shocks (IS) occurred in 7 patients (13.7%; mean 6.57±4 shocks per patient), 16.14±38 months after ICD implantation, and lead fracture was the first cause (n=4, 57.1%). The incidence of IS was higher in the asymptomatic patients (p=0.09). Device-related complications were similar in both groups (p=1). A total of 14 patients (27.4%) had =1 complications. The mean interval from implantation to a complication was 13.91±98 months. The most frequent complication was lead failure in 9 (17.6%). The risk of IS and device-complications at 3 years was 13.7% and 21.6% respectively, and eventually remains constant over the time. This study demonstrated that ICD has a high risk of complications, mainly during the early period after the device implantation. A higher rate of IS as well as a very low risk of arrhythmic events in asymptomatic BrS patients advocate to carefully evaluate this young and otherwise “healthy” population for the decision-making.

Side effects could certainly be decreased with lower dose of quinidine in asymptomatic Brugada patients, but what about efficacy? Author reply

We appreciate the letter from Marquez et al .1 regarding our article concerning the interest of hydroquinidine (HQ) in preventing ventricular arrhythmias in asymptomatic Brugada syndrome patients.2 In keeping with the first study published by our institution,3 the lower dose of HQ intake by patients was 600 mg/day in case of good tolerance. Hydroquinidine was increased to 900 mg/day if ventricular fibrillation (VF) was still inducible with a plasma level under the therapeutic range. …

Characteristics of Induced Ventricular Fibrillation Cycle Length in Symptomatic Brugada Syndrome Patients

Limited information is available on the ventricular fibrillation (VF) spectrum in Brugada syndrome (BS) patients. We clarified differences in the VF cycle length (CL) using fast-Fourier transformation (FFT) analysis in symptomatic and asymptomatic BS patients. VF was induced by pacing from the right ventricular (RV) apex and/or RV outflow tract (RVOT) for >8s. A 4096-point FFT analysis of results from 28 male BS patients (51.1 ± 13.7 years old) was performed. Dominant frequency (DF) from phases 1 (4s) to 6 was obtained at 2-s intervals. The average DF from surface and intracardiac electrograms (ECG: DF(ECG); ICE: DF(ICE,), respectively) was compared between symptomatic and asymptomatic patients. Symptomatic patients had a significantly shorter effective refractory period at a CL of 600 ms at the RVOT than asymptomatic patients. DF(ECG) significantly increased with phase (5.64 ± 0.32 Hz in phase 1 to 6.16 ± 0.52 Hz in phase 6) and was significantly higher in symptomatic patients than in asymptomatic patients. DF(ICE) had the same characteristics as DF(ECG). Induced VF in BS patients can be characterized using FFT analysis. Our data support the hypothesis that symptomatic patients have a significantly shorter VF CL than asymptomatic patients.

Brugada Syndrome 2012

Brugada syndrome (BS) is a cardiac disorder characterized by typical ECG alterations, and it is associated with a high risk for sudden cardiac death (SCD), affecting young subjects with structurally normal hearts. The prevalence of this disorder is still uncertain, presenting marked geographical differences. The syndrome has a genetic basis, and several mutations have been identified in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as in genes involved in the trafficking or regulation of these channels. Most BS patients are asymptomatic, but those who develop symptoms present with syncope and/or SCD secondary to polymorphic ventricular tachycardia and/or ventricular fibrillation. Risk stratification is still challenging, especially in cases of asymptomatic BS patients. This is a brief review of recent advances in our understanding of the genetic and molecular bases of BS, arrhythmogenic mechanisms and clinical course, as well as an update of the tools for risk stratification and treatment of the condition.