Calcium sensitizers in chronic heart failure: inotropic interventions-reservation to preservation

Newly developed Ca2+ sensitizers possess different mechanisms of action on contractile machinery. Increasing maximal Ca(2+)-activated force in addition to enhancing Ca2+ sensitivity (MCI-154, EMD 53998, and EMD 57033) could exert pronounced positive inotropy and may provide a mechanoenergetic advantage over the classic Ca2+ mobilization in the chronically failing heart. EMD 53998 and EMD 57033 prolong crossbridge attachment time, resulting in negative lusitropy. In contrast, pimobendan, levosimendan, and MCI-154 accelerate left ventricular relaxation in heart failure, because Ca2+ sensitizing action of these agents may be prominent during the early phases of contraction. Therefore, Ca2+ sensitizers can avoid the legacy of problems associated with conventional inotropic interventions and may break through "reservation" to "preservation" in the treatment of chronic heart failure.