Vagal stimulation in heart failure.

Vagal nerve stimulation (VNS) has a strong pathophysiological rationale as a potentially beneficial treatment for heart failure with reduced ejection fraction. Despite several promising preclinical studies and pilot clinical studies, the two large, controlled trials-NECTAR-HF and INOVATE-HF-failed to demonstrate the expected benefit. It is likely that clinical application of VNS in phase III studies was performed before a sufficient degree of understanding of the complex pathophysiology of autonomic electrical modulation had been achieved, therefore leading to an underestimation of its potential benefit. More knowledge on the complex dose-response issue of VNS (i.e., pulse amplitude, frequency, duration and duty cycle) has been gathered since these trials and a new randomized study is currently underway with an adaptive design and a refined approach in an attempt to deliver the proper dose to a more selected group of patients.