Abstract 14720: Novel Sodium Channel Voltage Sensor Mutation Leading to Unique Escape Capture Bigeminy Phenotype and Left Ventricular dysfunction
Introduction: Voltage sensor mutations may cause hypokalemic periodic paralysis. We report a sodium channel voltage sensor mutation producing dilated cardiomyopathy and a spectrum of arrhythmias with a unique electrocardiographic signature- junctional escape ventricular capture bigeminy.
Methods & Results: We investigated a family (figure A) with dilated cardiomyopathy and arrhythmias including atrial fibrillation, complete AV block, junctional rhythm and ventricular tachycardia (VT). The proband who received a defibrillator had atrial fibrillation and VT. The proband's mother had sick sinus syndrome and underwent pacemaker implantation. Uniquely, 4 affected members (proband, mother, maternal grandfather and uncle) had the same ECG pattern of junctional escape ventricular capture bigeminy (Figure D). At electrophysiologic testing, mapping of both ventricles revealed that both beats of the bigeminy originated in the IV septum inferiorly, with exits changing randomly between either side of the septum (Figure B). No single site responsible for the ectopic beats was demonstrated at mapping. There was no evidence of bundle branch reentry. The bigeminy was suppressed by intravenous sodium channel blocker lidocaine. Genetic analysis of 3 family members revealed the same novel gene mutation (R222Q) in the transmembrane portion of the cardiac sodium channel gene, SCN5A (nucleoside change was 665 G>A; Arg 222 Gln, located in S3-S4 voltage-sensor regions of Domain II). Patch-clamp studies revealed leftward (negative) shifts in current-voltage relationships, rapid inactivation kinetics, establishing a decreased threshold for channel opening especially in cells that hyperpolarize (Figure C).
Conclusions: Our results support the conclusion that shifts in sodium channel activation induced by mutations in the voltage-sensor leading to increased myocardial excitability should be considered in familial cardiomyopathy with escape capture bigeminy.
- © 2010 by American Heart Association, Inc.