Acute heart failure is a challenging medical crisis with inadequate drug options. Many patients experience the need for inotropic support, but typical therapeutic agents they increase cardiac output increase cardiac muscle intracellular calcium. Consequently, the energy and oxygen burden on the already metabolically compromised heart is increased and the likelihood of arrhythmias is enhanced as well. An attractive alternative are agents that directly target the sarcomere, an area ripe for therapeutic development for systolic heart failure in general. In Inotropes and inodilators for acute heart failure: sarcomere active drugs in focus, Drs. Nagy, Pollesello, and Papp provide an update on the status of novel drugs that increase heart contraction by sensitizing the contractile machinery to calcium or by directly activating cardiac myosin. These include Levosimendan and Pimobendan, which have other modes of action beneficial to the stressed heart, as well as Omecamtiv Mecarbil. Finally, this article explores the promise of innovative agents that target cardiac myofilaments, such as SR-33805 and the nitroxyl donor, CXL-1020, a compound that also enhances calcium turnover by the sarcoplasmic reticulum. This comprehensive review covers both the molecular aspects and clinical considerations of this cutting-edge area of drug development.
-George Booz, JCVP Assistant Editor
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