Searching for the ideal inotropic agent to rescue a failing heart

This editorial refers to ‘Beneficial effects of SR33805 in failing myocardium’ by Y. Ait Mouet al., pp. 412–419, this issue. Heart failure (HF) is a major international public health problem that is becoming epidemic as the population ages.1 Despite advances in treating HF in ambulatory patients, acute cardiac decompensation and failure remain associated with high rates of morbidity and death.1 Acute and decompensated end-stage HF cause low cardiac output that can be treated with positive inotropic agents to increase myocardial contractility.2 Conventional inotropic agents such as β-adrenergic agonists and phosphodiesterase inhibitors provide short-term haemodynamic improvement, but they do not improve prognosis.2,3 Such drugs increase cyclic AMP (cAMP) levels, which in turn increase intracellular Ca2+ levels and enhance contractility. Still, as high levels of intracellular Ca2+ are associated with increased energy consumption, arrhythmias, and myocardial cell death,4 these agents can worsen outcomes in HF patients.2,3 Consequently, novel strategies are needed to increase cardiac contractility and treat this debilitating illness.