Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure

Gaetano M. De Ferrari*, Harry J. G. M. Crijns, Martin Borggrefe, Goran Milasinovic, Jan Smid, Markus Zabel, Antonello Gavazzi, Antonio Sanzo, Robert Dennert, Juergen Kuschyk, Srdjan Raspopovic, Helmut Klein, Karl Swedberg, Peter J. Schwartz

*Corresponding author for this work

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Aims In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. Methods and results This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 +/- 11 years, LV ejection fraction (LVEF) 23 +/- 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P <0.001) in NYHA class quality of life, 6-minute walk test (from 411 +/- 76 to 471 +/- 111 m), LVEF (from 22 +/- 7 to 29 +/- 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. Conclusions This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.
Original languageEnglish
Pages (from-to)847-855
JournalEuropean Heart Journal
Issue number7
Publication statusPublished - Apr 2011


  • Heart failure
  • Autonomic nervous system
  • Non-pharmacologic therapy

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