Background: Clinical treatment of heart failure is still suffering from limited efficacy
and unfavorable side effects. The recently developed group of agents, the myosin motor activators,
act directly on cardiac myosin resulting in an increased force generation and prolongation
of contraction. The lead molecule, omecamtiv mecarbil is now in human 3 stage. In addition to
the promising clinical data published so far, there are new in vitro results indicating that the effect
of omecamtiv mecarbil on contractility is rate-dependent. Furthermore, omecamtiv mecarbil
was shown to activate cardiac ryanodine receptors, an effect that may carry proarrhythmic risk.
Methods: These new results, together with the controversial effects of the drug on cardiac oxygen
consumption, are critically discussed in this review in light of the current literature on omecamtiv
Results: In therapeutically relevant concentrations the beneficial inotropic effect of the agent is
not likely affected by these new results - in accordance with the good clinical data. At supratherapeutic
concentrations, however, activation of cardiac ryanodine receptors may increase
arrhythmia propensity, and the stronger effect on diastolic than systolic cell shortening, observed
at higher pacing frequencies, may decrease or offset the inotropic effect of omecamtiv
Conclusion: Further studies with definitely supratherapeutical concentrations of omecamtiv
mecarbil should be designed to map the actual risk of these potentially harmful side-effects.