Mechanical properties play a crucial role in many biological processes related to health and disease. In the heart, alterations in the extracellular matrix composition and cross-linking lead to stiffening of the cellular microenvironment during development. Additionally, myocardial infarction and cardiomyopathies cause fibrosis and a stiffer environment, impacting cardiomyocyte behavior. In this study, I discover that individual cardiomyocyte adhesions detect both fast oscillating cardiac and slow non-muscle myosin contractions simultaneously. This results in oscillating tension on the mechanosensitive adaptor protein talin when on substrates with the stiffness of healthy adult heart tissue, as opposed to no tension on embryonic heart stiffness and continuous stretching on fibrotic stiffness. Furthermore, I demonstrate that PKC activation induces cardiomyocyte hypertrophy in a stiffness-dependent manner through the activation of non-muscle myosin. Lastly, PKC and non-muscle myosin are upregulated at costameres in heart disease, suggesting that abnormal mechanosensing contributes to long-term remodeling and heart failure.