Abstract
Inotropes historically all increased intra-cellular calcium levels and they commonly caused intracellular Ca2+ overload and triggered malignant arrhythmias. The myosin activators, such as Omecamtiv Mecarbil (OM), increase myosin activity and function, and modify acto-myosin interaction through calcium-independent mechanisms. OM is a selective cardiac myosin activator that binds specifically the catalytic domain of cardiac myosin without any significant effect over other types of non-cardiac myosin. It increases the speed of ATP hydrolysis and, therefore, accelerates the transition rate to a strongly bound force-producing state, increases the number of myosin heads that interact with actin filaments and increases the proportion of time they are in a force producing state. OM decreases the inefficient use of non-contractile energy. OM has been studied in 4 phase II clinical trials with more than 1,300 patients with heart failure. The GALACTIC-HF trial is a nearly 8,000 patient HFrEF mortality/morbidity trial which started recruiting in January 2017 and should be completed soon.
Highlights
The term inotropes is used to describe all pharmacological agents that directly improve the contractile function of the heart.[1,2,3] agents that alter cardiac performance by modifying the cardiac calcium ion (Ca2+) balance and its flux into the cardiac myocyte are included under this definition.[4]
Omecamtiv Mecarbil (OM) is a selective cardiac myosin activator that binds the catalytic domain of cardiac myosin without any significant effect over other types of non-cardiac myosin. It increases the speed of adenosine triphosphate (ATP) hydrolysis and, accelerates the transition rate to a strongly bound force-producing state, increases the number of myosin heads that interact with actin filaments and increases the proportion of time they are in a force producing state
This study reported a dose-dependent improvement of cardiac systolic function parameters including left ventricular fractional shortening (LVFS 8±1%), left ventricular ejection fraction (LVEF, 7±1%), systolic ejection time (SET, 85±5 ms), stroke volume (SV, 15±2 mL)
Summary
The term inotropes is used to describe all pharmacological agents that directly improve the contractile function of the heart.[1,2,3] agents that alter cardiac performance by modifying the cardiac calcium ion (Ca2+) balance and its flux into the cardiac myocyte are included under this definition.[4]. Omecamtiv mecarbil increases the number of myosin heads that interact, in the force producing activity, with actin filaments during depolarization (see figure 1).
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