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 mecarbil.
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 mecarbil.
CONCLUSION: Further studies with definitely supratherapeutical concentrations of 
omecamtiv mecarbil should be designed to map the actual risk of these 
potentially harmful side-effects.