Rapid Publication Electrophysiological Abnormalities and Arrhythmias in a MHC Mutant Familial Hypertrophic Cardiomyopathy Mice

A new mouse cardiac electrophysiology method was used to study mice harboring an a -myosin heavy chain Arg403Gln missense mutation ( a -MHC 403/ 1 ), which results in histological and hemodynamic abnormalities characteristic of familial hypertrophic cardiomyopathy (FHC) and sudden death of uncertain etiology during exercise. Wild-type animals had completely normal cardiac electrophysiology. In contrast, FHC mice demonstrated ( a ) electrocardiographic abnormalities including prolonged repolarization intervals and rightward axis; ( b ) electrophysiological abnormalities including heterogeneous ventricular conduction properties and prolonged sinus node recovery time; and ( c ) inducible ventricular ectopy. These data identify distinct electrophysiologic abnormalities in FHC mice with a specific a -myosin mutation, and also validate a novel method to explore in vivo the relationship between specific genotypes and their electrophysiologic phenotypes. ( J. Clin. Invest. 1997. 99: 570–576.)