Malalignment of the sarcomeric filaments in hypertrophic cardiomyopathy with cardiac myosin heavy chain gene mutation

Objective-To investigate changes in the alignment of the sarcomeric filamen ts in hypertrophic cardiomyopathy and the effects of cardiac beta myosin he avy chain (beta-MHC) mutation on the sarcomeric ultrastructure. Design-A retrospective analysis. Patients-Endomyocardial biopsy samples were examined by transmission electr on microscopy in seven patients with hypertrophic cardiomyopathy and beta-M HC mutation, six with hypertrophic cardiomyopathy but without the mutation, and five controls (with chest pain syndromes). Main outcome measure-Alignment of the sarcomeric filaments and the distance between neighbouring thick myosin filaments. Results-In controls, cross sections of the sarcomere at the A band showed a highly organised orthohexagonal array with 6 thin actin filaments surround ing one thick myosin filament, whereas in hypertrophic cardiomyopathy the a lignment of the sarcomeric filaments was sparse and disrupted. In hypertrop hic cardiomyopathy with a mutation, the distance between neighbouring thick myosin filaments was greater than in controls (mean (SD) 45.3 (4.7) v 38.5 (3.5) nm, p < 0.05), and the variance of the distance was greater than in controls (8.0 (0.7) v 4.8 (1.0) nm, p < 0.001) or in patients with hypertro phic cardiomyopathy without a mutation (6.7 (0.6) nm, p < 0.05). In the lat ter, the variance of the distance was also greater than in the controls (p < 0.01). A significant correlation was found between the grade of the myocy te hypertrophy and the variance of the distance (r = 0.654; p < 0.01). Conclusions-The alignment of the sarcomeric filaments is disrupted in hyper trophic cardiomyopathy, particularly when there is beta-MHC mutation.