Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome: A Prospective Evaluation of 52 Families - Right Bundle Branch Block and ST-Segment Elevation Syndrome
Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome: A Prospective Evaluation of 52 Families.
What are the results of provocative testing and genetic analysis in symptomatic and asymptomatic individuals with the Brugada syndrome, and what is their prognosis?
Patients Enrolled: 60
Sixty individuals from 52 families were diagnosed as having the Brugada syndrome based on clinical and ECG criteria. Thirty of these patients had a history of cardiac arrest/syncope, and 30 were asymptomatic. Pharmacologic challenge with intravenous flecainide or ajmaline was performed in 41 patients, and 39 patients underwent electrophysiologic testing to determine whether ventricular tachycardia (VT) or fibrillation (VF) was inducible. Genetic analysis for mutations of the SCN5A gene was performed in 52 of the probands and in 44 family members who had no clinical evidence of the Brugada syndrome. The patients were treated according to physician preference (cardioverter/defibrillator [ICD] in 26 patients and drug therapy in five patients).
The pharmacologic challenge was positive (induction or worsening of ST elevation in V1-V3) in 85% of the patients. The test results were not reproducible in three of six patients in whom serial testing was performed. VT/VF was inducible in 67% of patients. The positive predictive value of inducible VT/VF for cardiac arrest/syncope during follow-up was 50%, and the negative predictive value was 46%. During a mean of 33 months of follow-up, the incidence of cardiac arrest/syncope was 29% in symptomatic patients, and 0% in the asymptomatic patients. A mutation of the SCN5A gene was found in 15% of the tested probands and in 45% of the tested asymptomatic family members. A drug challenge was positive in only 15% of silent gene carriers.
This is an important study because it challenges current views regarding the Brugada syndrome. From the clinical standpoint, perhaps the most important contrary finding is that asymptomatic patients are at low risk and need not necessarily be treated with an ICD. However, additional follow-up is needed to establish whether these patients maintain a benign prognosis beyond 3 years of follow-up.
1. Priori SG, Napolitano C, Gasparini M, et al. Circulation 2000;102:2509-15.
Keywords: Brugada Syndrome, Genetic Heterogeneity, Follow-Up Studies, Heart Conduction System, Ventricular Fibrillation, Syncope, Coronary Disease, Heart Arrest, Electrocardiography, Mutation, Prognosis, Tachycardia, Ventricular, Bundle-Branch Block, Flecainide, Defibrillators, Implantable
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