Empirically Based Guidelines for Selecting Vagus Nerve Stimulation Parameters in Epilepsy and Heart Failure

Vagus nerve stimulation (VNS) is a promising therapy to treat patients with epilepsy and heart failure. Outcomes of preclinical studies and clinical trials indicate that the selection of stimulation parameters has a direct impact on therapeutic efficacy and patient tolerability, suggesting that both the efficacy and tolerability of VNS could potentially be improved with a change in stimulation parameters. In this review, the success of translating stimulation parameters for epilepsy and heart failure from preclinical studies in animal models to human use in the clinic is evaluated on the basis of patient outcomes and stimulation-induced side effects. Data suggest that patients receiving VNS for epilepsy may experience improved seizure reduction by increasing the frequency and/or duty cycle of stimulation as well as incorporating closed-loop systems to deliver stimulation closer to seizure onset. Further, data suggest that VNS for heart failure is limited by the inability to activate the nerve fibers mediating therapeutic benefit without co-activation of side effect-inducing fibers. This may explain why pivotal trials of VNS for heart failure failed to meet primary efficacy outcomes despite promising preclinical outcomes in animal models. Improved characterization of the relationship between the stimulation parameter space and recruitment of the underlying fiber populations will likely expand the use of VNS to treat a variety of diseases and also improve upon current understanding of the mechanisms of action underlying VNS.