Gender Differences in Passive Tension in Hypertrophic Cardiomyopathy Patients

Abstract

BackgroundHypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder with a prevalence of 1:500. In ∼65% of all HCM patients the causative mutation is identified. HCM patients that are sarcomere-mutation negative tend to have a less severe phenotype. Mutations in the MYBPC3 and MYH7 genes encoding cardiac myosin-binding protein C (cMyMP-C) and β-myosin heavy chain (MyHC) represent >80% of all genotyped HCM cases. HCM is characterized by asymmetric hypertrophy of the left ventricle and diastolic dysfunction. In the present study we investigated if passive stiffness of the sarcomeres may underlie diastolic dysfunction.MethodsIn-vitro passive tension measurements were done at sarcomere lengths of 1.8 to 2.2μm in cardiomyocytes from 10 sarcomere mutation-negative patients(SMN: 5 male, 5 female), 17 patients carrying a MYBPC3 mutation(MYBPC3: 10 male, 7 female), and 10 patients carrying a MYH7 mutation (MYH7: 5 male, 5 female). Tissue was obtained during myectomy surgery from the interventricular septum. Cardiomyocytes were mechanically isolated and Triton-permeabilized.ResultsPassive tension over the entire range of sarcomere lengths did not differ between sarcomere-mutation positive and mutation-negative male HCM patients. Passive tension in myocytes from sarcomere mutation-positive women was significantly higher compared to female mutation-negative HCM patients. Female MYH7 cardiomyocytes showed a higher sarcomere stiffness compared to male MYH7.ConclusionOur measurements suggest that high sarcomere passive stiffness may contribute to diastolic dysfunction in female HCM patients harboring a mutation in genes encoding thick filament proteins.