Impaired myocardial relaxation is multifactorial and reflects a balance between the active processes responsible for calcium sequestration and removal from the cytosol, and physical factors responsible for loaddependent relaxation. In hypertrophy and heart failure, the slowing of the calcium transient (principally due to slowed sarcoplasmic reticulum calcium uptake) allows the slowed rate of calcium sequestration to dominate the rate of relaxation. This process is exacerbated at higher rates of stimulation where incomplete recovery of the calcium transient occurs between beats, and this in turn elevates end-diastolic pressure. The latter may be compounded by structural changes in the myocardium that increase stiffness. The profound neurohormonal and paracrine changes that accompany cardiac hypertrophy and failure also contribute to changes in calcium cycling, the responsiveness of the myofilaments to calcium, and ultimately to diastolic dysfunction...