The following is a summary of “Effect of the Novel Myotrope Danicamtiv on Cross‐Bridge Behavior in Human Myocardium,” published in the October 2023 issue of Cardiology by Choi et al.

This research investigates the distinct impact of omecamtiv mecarbil (OM) and danicamtiv, both myosin activators within the cardiac sarcomere, on myocardial force output. While both compounds elevate force generation by selectively stimulating myosin, a comprehensive comparison of their molecular mechanisms remains elusive.

Using chemically skinned myocardial samples exposed to varying Ca²⁺ solutions, the study assessed OM and danicamtiv’s influence on the sensitivity of force generation. Findings indicated that OM notably raised Ca²⁺ sensitivity, whereas danicamtiv exhibited similar sensitivity to untreated samples. Directly comparing OM and danicamtiv’s effects on dynamic cross-bridge behavior at concentrations yielding similar force increases at submaximal levels (pCa 6.1), both compounds slowed cross-bridge detachment rates from the strong-bound state and recruitment into the force-producing state. However, OM substantially prolonged the time for force relaxation initiation and subsequent force generation after rapid stretch, a phenomenon markedly lessened in danicamtiv-treated myocardium.

This study marks the first direct comparison between OM and danicamtiv regarding cross-bridge kinetics. Notably, at a comparable level of force enhancement, danicamtiv exhibited a less pronounced impact on slowing cross-bridge kinetics than OM. As a result, danicamtiv may offer similar systolic function improvement as OM without excessively prolonging systolic ejection time or impeding cardiac relaxation, thus potentially aiding diastolic filling at the whole-organ level.

Source: ahajournals.org/doi/10.1161/JAHA.123.030682