The importance of class-I antiarrhythmic drug test in the evaluation of patients with syncope: unmasking Brugada syndrome.

INTRODUCTION: The Brugada syndrome (BrS) can first present with syncope. Class-I antiarrhythmic drug (AAD) test is used to unmask the diagnostic coved-type ECG pattern in case it is not spontaneously present. The aim of the study was to analyze patients with BrS presenting with syncope as first manifestation and compare patients with syncope and a spontaneous coved-type ECG to patients with syncope in whom a class-I AAD test unmasked the disease. METHODS AND RESULTS: Fifty-eight of 157 probands (36.9%) had syncope as first manifestation of the disease. Twenty-six patients (44.8%, group A) showed a spontaneous coved-type ECG diagnostic for BrS at first presentation. In 32 patients (55.2%, group B) without spontaneous coved-type ECG pattern at first presentation (36% normal ECGs and 19% type-II ECG pattern), a class-I AAD test unmasked the disease. Twenty-one patients of group A and 29 patients of group B underwent implantable cardioverter defibrillator (ICD) implantation. The mean follow up as 9.7 ± 55.7 month. Four patients in group A (15.4%) and 3 patients (9.3%) in group B had appropriate ICD shock delivery due to ventricular fibrillation or ventricular tachycardia (P = NS). CONCLUSION: One of 3 patients with BrS presents first with syncope. More than one-third of these patients have a normal ECG at investigation for syncope and the correct diagnosis would have been missed without a class-I AAD test. Patients presenting with syncope are at similar risk irrespective of the presence of a spontaneous coved-type ECG.

Ajmaline challenge in young individuals with suspected Brugada syndrome.

BACKGROUND: The clinical characteristics and the results of ajmaline challenge in young individuals with suspected Brugada syndrome (BS) have not been systematically investigated. METHODS: Among a larger series of patients included in the BS database of our Department, 179 patients undergoing ajmaline challenge were included in the study and categorized in two groups according to age: group 1 (<18 years old) and group 2 (≥18 years old). Clinical features and results of the ajmaline challenge of each group were compared. RESULTS: Young individuals were more often asymptomatic compared to adult patients (P = 0.002). They showed a higher number of normal ECGs (P = 0.023), a lower percentage of Brugada type II electrocardiographic pattern compared to the adult population (P = 0.011), and a comparable amount of spontaneous Brugada type III electrocardiographic pattern (P = 0.695). Ajmaline provoked a higher degree of intraventricular conduction delay (P = 0.002) and higher degree of prolongation of the ventricular repolarization phase (P = 0.013) in young individuals but its pro-arrhythmic risk was comparable in the two groups (P = 0.684). Furthermore, inducibility of ventricular arrhythmias in young patients with a positive ajmaline test was comparable to that of the adults with a positive ajmaline test (P = 0.694). CONCLUSIONS: The present study demonstrates the low-risk profile of the ajmaline test in young patients when performed by experienced physicians and nurses in an appropriate environment.

Number of electrocardiogram leads displaying the diagnostic coved-type pattern in Brugada syndrome: a diagnostic consensus criterion to be revised.

AIMS: According to the diagnostic consensus criteria, the electrocardiographic (ECG) diagnosis of Brugada syndrome requires coved-type > or =2 mm ST-segment elevation in >1 right precordial lead (RPL) V1-V3 in the presence or absence of a sodium-channel blocker. However, this consensus has not been evaluated. We aimed to assess the distribution of coved-type ST-segment elevation on RPLs in a large patient cohort to reevaluate the appropriateness of the diagnostic consensus criteria. METHODS AND RESULTS: We included 186 individuals with spontaneous and/or drug-induced ECGs of coved-type > or =2 mm ST-segment elevation in at least one RPL. A total of 376 ECGs were analysed for the number, distribution and maximal J-point elevation of diagnostic RPLs. Among all ECGs, 27 (7%) showed a coved-type pattern in 3 RPLs, 205 (55%) in 2 RPLs, and 144 (38%) in only 1 RPL. Leads V1 and V2 were diagnostic in 99% of all ECGs with two diagnostic RPLs. Lead V3 alone was not diagnostic in any ECG. Maximal J-point elevation was significantly higher in lead V2 than V1. Sixty case subjects (32%) had only ECGs with one RPL displaying a coved-type ST-segment elevation. There was no significant difference in clinical presentation and outcome compared with the 126 Brugada patients with ECGs displaying >1 diagnostic RPL. Major arrhythmic events occurred with the same rate (8%) in both groups during a follow-up >5 years. CONCLUSION: Lead V3 does not yield diagnostic information in Brugada syndrome. Individuals with ECGs displaying only one diagnostic RPL have a similar clinical profile and arrhythmic risk as Brugada patients with ECGs displaying >1 diagnostic RPL. Revision of the consensus criteria should be considered.

Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome.

BACKGROUND: Repolarization abnormalities in the inferior-lateral leads in Brugada syndrome (BS) have not been systematically investigated. METHODS AND RESULTS: 280 patients (age, 41+/-18 years; 168 males) with BS were screened for inferior-lateral repolarization abnormalities. The repolarization abnormalities were classified either as early repolarization pattern or coved > or = 2-mm Brugada pattern and as spontaneous or class I antiarrhythmic drug (AAD) induced. Thirty-two patients (11%) had inferior-lateral spontaneous early repolarization pattern. These patients were less likely to be asymptomatic at first presentation (13 of 32 versus 156 of 248 patients, P=0.02), and spontaneous type I ECG was more frequent among them (38% versus 21%, P=0.05). The spontaneous early repolarization pattern occurred more frequently among patients with BS than in 283 family members not having BS (11% versus 6%, P=0.03). Class I AAD administration provoked inferior-lateral coved Brugada pattern in 13 patients with BS. These patients had longer baseline PR intervals (206+/-48 versus 172+/-31 ms, P<0.001) and class I AAD-induced QRS interval prolongation (108 to 178 versus 102 ms to 131 ms, P<0.001). In 3 patients, the class I AAD-provoked coved Brugada pattern was only present in the inferior leads. CONCLUSIONS: Inferior-lateral early repolarization pattern occurs spontaneously relatively frequently in BS. These patients have a more severe phenotype. Class I AAD administration provokes inferior-lateral coved Brugada pattern in 4.6% of patients. We report for the first time 3 patients in whom the class I AAD-provoked coved Brugada pattern was only observed in the inferior leads.

Genetic modulation of brugada syndrome by a common polymorphism.

BACKGROUND: Brugada syndrome predisposes some subjects to ventricular tachyarrhythmias and sudden cardiac death. Mutations in SCN5A gene have been associated with approximately 25% of Brugada syndrome patients. A common variant in SCN5A, H558R has shown to improve sodium channel activity in mutated channels. We studied whether common variant H558R has any clinical implications in the phenotype of Brugada syndrome. METHODS: Our study population consisted of Brugada syndrome subjects 75 with SCN5A mutation and 92 without SCN5A mutation. Their mean age was 39 +/- 15 and 42 +/- 17 years, and 65% and 86% were male, respectively. We measured PR-, QRS-, QTc-intervals from leads II and V2 of the 12-lead ECG. We also evaluated J-point amplitude from lead V2 and R'/S ratio from lead aVR (the "aVR sign"). The H558R (A-->G) genotype was detected with direct sequencing of the SCN5A gene. RESULTS: The AA genotype carriers had longer QRS duration in lead II (P = 0.017) and higher J-point elevation in lead V2 (P = 0.013), higher "aVR sign" (P = 0.005) and a trend toward more subjects with symptoms (P = 0.067) than G allele carriers. None of the results were significant in Brugada syndrome subjects without SCN5A mutation. CONCLUSION: The common variant H558R seems to be a genetic modulator of Brugada syndrome among carriers of a SCN5A mutation, in whom the presence of the less common allele G improves the ECG characteristics and clinical phenotype.