Figure 1.

Schematic representation of heart failure due to sarcomeric/intrasarcomeric mutations. Mutations in the proteins responsible for the maintenance of sarcomere structure and function result in inefficient or excessive use of ATP and a consequent energy deficiency. The energy requirements then compromise calcium homeostasis in the cell, resulting in, among other events, an increase in calcium sensitivity of the ATPase SERCA and increased cytosolic free calcium. The contractibility of the myocyte is then compromised, ultimately resulting in cell death and consequent myocardial fibrosis. This myocardial fibrosis and further ischemia may result in left ventricular hypertrophy, increasing the risk of heart failure.

Abbreviations: NCX, sodium–calcium exchanger; DHPR, dihydropyridine receptor; Ryr, ryanodide receptor; SERCA, sarco/endoplasmic reticulum Ca2⁺-ATPase; AMP, adenosine monophosphate; ATP, adenosine triphosphate.