**4. Molecular mechanisms of left heart failure**

All cell types within the heart respond to stress, including in response to chronic pressure overload [60]. However, the majority of research has focused on changes within the myocytes as they are the primary cell type responsible for contraction and heart failure is a disease of impaired cardiac function. The hallmark molecular change of myocyte remodeling is hypertrophy. In response to pathological load such as pressure overload, myocyte size increases via synthesis of new sarcomeres. Myocytes also reactivate a fetal program of gene expression, now often referred to as the hypertrophic gene program [61]. While initially characterized in the failing left heart, the fetal (hypertrophic) gene program has now been shown to also occur in RV failure [62]. While believed to be compensatory at first, over time this is maladaptive, and likely contributes to the energy deficit of the failing heart.
