Muscle dysfunction in hypertrophic cardiomyopathy: What is needed to move to translation?

Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere genes. As such, HCM provides remarkable opportunities to study how changes to the heart’s molecular motor apparatus may influence cardiac structure and function. Although the genetic basis of HCM is well-described, there is much more limited understanding of the precise consequences of sarcomere mutations—how they remodel the heart, and how these changes lead to the dramatic clinical consequences associated with HCM. More precise characterization of the mechanisms leading from sarcomere mutation to altered cardiac muscle function is critical to gain insight into fundamental disease biology and phenotypic evolution. Such knowledge will help foster development of novel treatment strategies aimed at correcting and preventing disease development in HCM.