Toward Safe Inotropic Therapy

The use of currently available positive inotropic agents is associated with an unfavorable clinical outcome. The disappointment with positive inotropic therapy is to some extent foreseeable as currently available inotropic agents may precipitate ventricular arrhythmias due to a diastolic rise in intracellular Ca, trigger/worsen myocardial ischemia due to an increased oxygen demand, and foster fuel deprivation from an energy starved heart. Safe use of presently available inotropic agents and development of novel inotropic agents must ensure that they are not associated with a diastolic rise in intracellular Ca, an increase in myocardial oxygen consumption, and energy expenditure. Agents that improve left ventricular systolic performance through prolongation of left ventricular ejection time and not through increased myocardial contractility, that is, myosin activators, may be associated with a favorable outcome as they do not affect diastolic intracellular Ca, myocardial oxygen demand, and presumably fuel expenditure.