Omecamtiv Mecarbil Improves Contraction Behaviour in a 3D Electromechanical Tissue Model of Heart Failure

Inotropic drugs, such as Omecamtiv Mecarbil (OM), are a promising treatment option for patients with heart failure with reduced ejection fraction. However, there are limited computational models available of fully coupled electromechanics (EM) and OM. We present a 3D EM model to simulate inotropic drug effects to assess pharmacological mechanisms and effects on human cardiac tissue. This fully coupled 3D EM open-source solver (SimCardEMS) was used to simulate healthy and failing tissue slabs. A model of OM behaviour was created by using experimental data to parametrize the cell model to replicate stabilisation of the pre-powerstroke state of myosin. The OM model replicates experimentally observed concentration dependent drug effects such as increased active tension with minimal effect on calcium transient. Therapeutic concentration of OM (0.2 µM) increased active tension by 33% in heart failure tissue. Total displacement was reduced in heart failure, but was partially recovered in the presence of 0.2 µM OM. However, the characteristic delay in time to peak contraction was not reflected in these results. These simulations enable detailed assessment of drug mechanisms and indicate that the model of OM in tissue EM requires further development to better represent the pharmacological effect.