Sarcomere Active Drugs in Focus

Abstract: Acute heart failure (AHF) emerges as a major and growing epidemiological concern with high morbidity and mortality rates. Current therapies in patients with acute heart failure rely on different strategies. Patients with hypotension, hypoperfusion, or shock require inotropic support, whereas diuretics and vasodilators are recommended in patients with systemic or pulmonary conges-tion. Traditionally inotropic agents, referred to as Ca2+ mobilizers load the cardiomyocyte with Ca2+ and thereby increase oxygen con-sumption and risk for arrhythmias. These limitations of traditional inotropes may be avoided by sarcomere targeted agents. Direct acti-vation of the cardiac sarcomere may be achieved by either sensitiz-ing the cardiac myofilaments to Ca2+ or activating directly the cardiac myosin. In this review, we focus on sarcomere targeted inotropic agents, emphasizing their mechanisms of action and over-view the most relevant clinical considerations. Key Words: acute heart failure syndrome, Ca2+ mobilizer, sarco-mere targeted agent, levosimendan, omecamtiv mecarbi