Reduced Myofilament Contraction in Human Heart Failure. Insights From Electromechanical Simulations

Intracellular Ca 2+ is the main activator of myofilament contraction and the altered Ca 2+ handling observed in failing cells has been established as the leading cause of reduced inotropy in heart failure. Electrophysiological studies usually quantify Ca 2+ transients to estimate contractile effects. However, heart failure remodeling of myofilaments also occurs, modifying the correlation between Ca 2 + and force. The aim of this study was to analyze myofilament tension generated by action potentials in human heart failure. In a ventricular electromechanical we investigated cellular contraction force associated with intracellular Ca 2+ in heart failure by implementing the characteristic electrophysiological,β-adrenergic, and mechanical changes. Despite the inotropic myofilament remodeling induced by heart failure, the maximal active tension in failing cells was one third of the force generated in normal cells. With isoproterenol,β-adrenergic stimulation increased systolic Ca 2+ , which enhanced myofilament tension by up to 150%, but failing cells also showed a smaller contraction force compared to normal. We observed that contractility was very sensitive to changes in intracellular Ca 2+ , confirming that increasing Ca 2+ peak would improve contraction in heart failure.