The energetic cost of contraction is higher in the myocardium of patients with hypertrophic cardiomyopathy

This editorial refers to ‘Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations’ by E.R. Witjas-Paalberends et al. , doi:10.1093/cvr/cvu127. Hypertrophic cardiomyopathy (HCM) is a disease characterized by a hypertrophied left ventricle (LV) in the absence of any overt cause and by an increased incidence of arrhythmias and cardiac sudden death. The subset of HCM patients with familial hypertrophic cardiomyopathy (FHC) displays a highly variable phenotype ranging from no symptoms to overt cardiomyopathy with early onset sudden cardiac arrest. This variability has made it difficult to identify any unifying mechanism that would lead to designing new approaches for diagnosis and therapy.Most of the several hundred mutations associated with HCM/FHC occur in sarcomeric proteins, and roughly half of them reside in two proteins: myosin and cardiac myosin-binding protein C (cMyBP-C). One hypothesis for a unifying mechanism underlying HCM/FHC is that the energetic cost of contraction is higher in the myocardium of HCM/FHC patients: the free energy released from the hydrolysis of ATP by myosin is used less efficiently to generate force at the whole heart level. The article by Witjas-Paalberends and Guclu (co-first authors) and their colleagues appearing in this issue1 makes a significant contribution supporting this hypothesis. Before commenting on their results, we will briefly review the properties of myosin and cMyBP-C and their history in the HCM/FHC literature.Myosin has many functions: …