CalciumSensitizers

Calcium sensitizers are a pharmacologic class of inotropes that increase cardiac contractility by increasing the sensitivity of the myocardium to calcium rather than increasing intracellular calcium concentration. The principal mechanism is binding to the calcium-bound form of troponin C, enhancing cross-bridge formation at a given calcium level. Some agents also cause vasodilation through other mechanisms (e.g., opening ATP-sensitive potassium channels).

Levosimendan is a prominent human medicine in this class, acting as a calcium sensitizer and vasodilator (inodilator). It is typically given by IV infusion for acute decompensated heart failure in several European and other countries; it has a long-acting metabolite that contributes to sustained effects after infusion. Pimobendan is a veterinary calcium sensitizer that also inhibits phosphodiesterase III, increasing cAMP and causing vasodilation; it is widely used in dogs with congestive heart failure and is not approved for human use.

Clinical considerations: Calcium sensitizers can improve hemodynamics with less increase in myocardial oxygen consumption than conventional catecholamine inotropes. However, hypotension from vasodilation, tachyarrhythmias, and uncertain long-term outcomes limit their use. Levosimendan’s FDA status in the United States was not approved as of 2024, while it is approved in the EU and other regions. Pimobendan is approved for veterinary use; its human data remain limited.