Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited arrhythmia syndrome in which drug therapy is often ineffective. We discovered that flecainide prevents arrhythmias in a mouse model of CPVT by inhibiting cardiac ryanodine receptor-mediated Ca(2+) release and thereby directly targeting the underlying molecular defect. Flecainide completely prevented CPVT in two human subjects who had remained highly symptomatic on conventional drug therapy, indicating that this currently available drug is a promising mechanism-based therapy for CPVT.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Arrhythmia Agents / therapeutic use
-
Arrhythmias, Cardiac / prevention & control
-
Calcium / physiology
-
Child
-
Flecainide / therapeutic use*
-
Heart Rate / drug effects
-
Humans
-
Male
-
Mice
-
Polymorphism, Genetic
-
Ryanodine Receptor Calcium Release Channel / drug effects
-
Ryanodine Receptor Calcium Release Channel / physiology
-
Syndrome
-
Tachycardia, Ventricular / genetics*
-
Tachycardia, Ventricular / prevention & control*
Substances
-
Anti-Arrhythmia Agents
-
Ryanodine Receptor Calcium Release Channel
-
Flecainide
-
Calcium