Sodium Channel Molecular Conformations and Antiarrhythmic Drug Affinity
TRENDS IN CARDIOVASCULAR MEDICINE
Authors: Sheets, Michael F.; Fozzard, Harry A.; Lipkind, Gregory M.; Hanck, Dorothy A.
Abstract
Class I cardiac antiarrhythmic drugs, for example, lidocaine, mexiletine, flecainide, quinidine, and procainamide, continue to play an important role in the therapy for cardiac arrhythmias because of the presence of use-dependent block. Lidocaine, as well as related drugs such as mepivacaine, bupivacaine, and cocaine, also belong to the class of medications referred to as local anesthetics. In this review, we will consider lidocaine as the prototypical antiarrhythmic drug because it continues to be widely used both as an antiarrhythmic drug (first used as an antiarrhythmic drug in 1950) as well as a local anesthetic agent. Both of these clinical uses depend upon block of sodium current (I-Na), but it is the presence of use-dependent I-Na block, that is, an increasing amount of block at faster heart rates, which enables a local anesthetic agent to be a useful antiarrhythmic drug. Although many early studies investigated the action of antiarrhythmic drugs on Na currents, the availability of site-directed mutant Na channels has enabled for major advances in understanding their mechanisms of action based upon molecular conformations of the Na channel. (Trends Cardiovasc Med 2010;20:16-21) (C) 2010, Elsevier Inc.
Cohort of Patients Referred for Brugada Syndrome Investigation in an Electrophysiology Service-19-Year Registry
ARQUIVOS BRASILEIROS DE CARDIOLOGIA
Authors: Warpechowski Neto, Stefan; Luz Leiria, Tiago Luiz; Gaudic Ley, Laura Lessa; Gaudie Ley, Antonio Lessa; Dutra, Luiza Zwan; Pires, Leonardo Martins; Kruse, Marcelo Lapa; de Lima, Gustavo Glotz
Abstract
Background: Brugada syndrome (SBr) is an arrhythmic condition characterized by ST-T segment abnormalities in the right precordial leads associated with a high risk of ventricular arrhythmias and sudden death. Local data regarding the clinical characteristics of patients with a typical electrocardiographic (ECG) pattern undergoing electrophysiological study are scarce. Objective: To evaluate patients with an ECG pattern suggestive of SBr referred for electrophysiological evaluation in a specialized center. Methods: Cohort study of patients referred for electrophysiological study because of an ECG pattern compatible with SBr between January 1998 and March 2017. Results: Of the 5506 procedures, 35 (0.64%) were for SBr investigation, 25 of which (71.42%) were performed in men. The mean age was 43.89 +/- 13.1 years. The ECG patterns were as follows: type I, 22 (62.85%); type II, 12 (34.30%); and type III, 1 (2.85%). Twenty-three patients (65.7%) were asymptomatic, 6 (17.14%) had palpitations, 5 (14.3%) had syncope, and 3 (8.6%) had a family history of sudden death. Electrophysiological study induced ventricular tachyarrhythmias in 16 cases (45.7%), the mean ventricular refractory period being 228 +/- 36 ms. Ajmaline / procainamide was used in 11 cases (31.4%), changing the ECG pattern to type I in 7 (63.6%). Sixteen cases (45.7%) received an implantable cardioverter defibrillator (ICD). In a mean 5-year follow-up, 1 of the 16 patients (6.25%) with ICD had appropriate therapy for ventricular fibrillation. There was no death. Other arrhythmias occurred in 4 (11.4%) cases. Conclusions: Most patients are men, and a type I ECG pattern is the main indication for electrophysiological study. Class IA drugs have a high ECG conversion rate. The ICD event rate was 6%.