Since EMD-57033 can activate the myosin heads from both the biochemically-defined SRX and the structurally-defined OFF states, synergistically, with activating the troponin complex, it can provide a proof of concept to guide the search for other small molecule muscle activators with similar properties that can correct the decline in contractile functions associated with heart failure, without significantly impairing the ventricular filling in diastole. Here, MYH14 is linked to heart failure.