In the last two decades, the autonomic imbalance characterized by vagal withdrawal and sympathetic increase has been shown to play a major role in the progression and prognosis of heart failure. Therefore, modulation of the autonomic nervous system (neuromodulation) with the aim to restore autonomic balance is gaining increasing interest as a potential therapy for patients with heart failure. Recently, different non-pharmacological approaches to neuromodulation have been evaluated in phase II and III clinical trials. Electrical vagus nerve stimulation is the most studied. This technique showed excellent results in preclinical studies, but at present the clinical experience is limited to a few studies, the results of which are apparently conflicting.This review discusses the preclinical and clinical experience of vagal stimulation in heart failure, in order to help understand the complexity of the methodology and our still limited knowledge of the dose-response relationship, which make difficult to interpret and compare the results of studies conducted with different designs and evaluating different devices and stimulation protocols.
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