Echocardiographic Strain Imaging to Assess Early and Late Consequences of Sarcomere Mutations in Hypertrophic

Background—Genetic testing identifies sarcomere mutation carriers (G+) before clinical diagnosis of hypertrophic cardiomyopathy (HCM), allowing characterization of initial disease manifestations. Prior studies demonstrated that impaired relaxation develops before left ventricular hypertrophy (LVH). The precise impact of sarcomere mutations on systolic function in early and late disease is unclear. Methods and Results—Comprehensive echocardiography with strain imaging was performed on 146 genotyped individuals with mutations in 5 sarcomere genes. Contractile parameters were compared in 68 preclinical (G+/LVH−), 40 overt (G+/LVH+) HCM subjects, and 38 mutation (−) normal control relatives. All subjects had normal LV ejection fraction (EF). In preclinical HCM, global and regional peak systolic strain (εsys) and longitudinal systolic strain rate (SSR) were not significantly different from controls, but early diastolic mitral annular velocity (Ea) was reduced by 13%. In overt HCM, there was a significant 27 % and 14 % decrease in global longitudinal εsys and SSR respectively, compared with both preclinical HCM and controls (p<0.013 for all comparisons), and a 33 % reduction in Ea