Cardiac contractility modulation (CCM) is a device-based therapy technique that has been shown to enhance cardiac contraction. However, its underlying mechanisms are understood incompletely. In this study, we employed a computational cell model to investigate the response to CCM-like pacing in a population of 435 different heart failure parametrizations. CCM-like pacing increased calcium transient and contraction amplitude in the full population.
Calcium influx through L-type calcium channels was increased starting at the first CCM beat. Both calcium release from and calcium uptake to the sarcoplasmic reticulum were enhanced during CCM-like pacing. Our simulations mechanistically reproduce key qualitative observations reported in literature and support the hypothesis that the positive inotropic effect of CCM is primarily a result of increased calcium cycling.