Exercise-induced left ventricular systolic dysfunction in women heterozygous for dystrophinopathy

Background: Mutations in the X-linked gene encoding dystrophin cause skeletal and cardiac muscle diseases in men. Female "carriers" also can develop overt disease. The purpose of this study was to ascertain the prevalence of cardiac contractile abnormalities in dystrophinopathy carriers.

Methods: Twenty-four dystrophinopathy heterozygotes and 24 normal women each underwent standard exercise stress echocardiography.

Results: Heterozygotes demonstrated mildly lower left ventricular ejection fractions (LVEFs) at rest compared with controls (0.56 + or - 0.10 vs 0.62 + or - 0.07, P = .02). After exercise, the mean LVEF fell to 0.53 + or - 0.14 in heterozygotes but rose to 0.73 + or - 0.07 in controls (P < .001). Twenty-one of 24 dystrophinopathy heterozygotes demonstrated > or = 1 of the following: abnormal resting LVEF, abnormal LVEF response to exercise, or exercise-induced wall motion abnormality.

Conclusions: Women heterozygous for dystrophinopathy demonstrate significant left ventricular systolic dysfunction, which is unmasked by exercise. This finding has mechanistic implications for both inherited and acquired cardiac disease states.