Familial hypertrophic cardiomyopathy mice display gender differences in electrophysiological abnormalities

Genetically-manipulated mice harboring an alpha-myosin heavy chain Arg403Gl n missense mutation (alpha-MHC403/+) display a phenotype characteristic of familial hypertrophic cardiomyopathy (FHC). Male and female (30 +/- 8 week old) heterozygous alpha-MHC403/+ mice and littermate controls were evaluate d using a surface electrocardiogram (ECG) and an in vivo cardiac electrophy siology study (EPS). Wild type animals had normal intracardiac electrophysi ology, with no significant differences between male and female control mice during EPS. The female mild-type mice did have slower heart rates and long er ECG intervals than their male wild-type counterparts. The female alpha-M HC403/+ mice had similar ECG's, cardiac conduction times, and refractory pe riods compared with female wild-type mice. In contrast, male FHC mice had d istinctive ECG and electrophysiologic abnormalities including right axis de viation, prolonged ventricular repolarization and prolonged sinus node reco very times. During programmed ventricular stimulation, 62%, of male alpha-M HC403/+ mice and 28% of female alpha-MHC403/+ mice had inducible ventricula r tachycardia. These studies identify gender specific electrophysiologic ab normalities in alpha-MHC403/+ FHC mice, concordant with the histological an d hemodynamic derangements previously reported.