Vagal stimulation for the treatment of heart failure: a translational success story
- Peter J Schwartz1,2,3,4
- 1Department of Molecular Medicine, University of Pavia, Pavia, Italy
- 2Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy
- 3Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, South Africa
- 4Chair of Sudden Death, Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Correspondence to Peter J Schwartz, Professor & Chairman, Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo V. le Golgi, 19 27100 Pavia, Italy;
One of the most inspiring features of medicine is the unending quest for better treatments for the affected patients. This is also the area where experimental and clinical medicine can merge and give rise to translational research. As far as heart failure is concerned, there have been interesting developments. Here, I will review the background that has prompted the initial attempts to modulate autonomic activity, and I will discuss the most recent data and current directions.
Heart failure is characterised by an autonomic imbalance with the combination of sympathetic upregulation and parasympathetic withdrawal, associated with progressive ventricular remodelling, arrhythmia generation and disease progression.1 This type of autonomic imbalance can be quantified at clinical level by baroreflex sensitivity, or by heart rate variability, and is associated with increased mortality after myocardial infarction,2–4 and in heart failure.5 ,6 Acute cardiac decompensation in patients with heart failure is often preceded by signs of further vagal withdrawal.7 Although β-blockers can be used to modify the impact of elevated levels of norepinephrine and the effects of augmented sympathetic tone, the ability of drug therapy to influence parasympathetic function is limited.
These considerations could not be separated by the evidence that increases in vagal activity, either by exercise training8 ,9 or by direct electrical vagal stimulation,10 have a powerful antifibrillatory effect, and can reduce sudden cardiac death. Altogether, they have provided a strong rationale for the evaluation of the potential benefit of chronic vagal stimulation in patients with heart failure.
Potential doubts towards the implementation of a non-traditional treatment were progressively dismissed by the evidence of a clear benefit in different animal models for heart failure,11 and by the fact that chronic vagal stimulation has been used without complications in a very high number of patients with …