[HTML][HTML] The vagus nerve and autonomic imbalance in heart failure: past, present, and future

PJ Hauptman, DL Mann - Heart failure reviews, 2011 - Springer
Heart failure reviews, 2011Springer
Advances in heart failure (HF) therapeutics over the last 20 years have led to widespread
acceptance and use of oral antagonists of the renin–angiotensin–aldosterone (RAAS) and
sympathetic nervous (SNS) systems [1, 2] in patients with a depressed ejection fraction. In
addition, implantable cardioverter defibrillators and cardiac resynchronization devices (CRT)
have been widely adopted in both practice guidelines and clinical care [3–5]. Nevertheless,
with the aging of the population and rising disease prevalence, interest in the development …
Advances in heart failure (HF) therapeutics over the last 20 years have led to widespread acceptance and use of oral antagonists of the renin–angiotensin–aldosterone (RAAS) and sympathetic nervous (SNS) systems [1, 2] in patients with a depressed ejection fraction. In addition, implantable cardioverter defibrillators and cardiac resynchronization devices (CRT) have been widely adopted in both practice guidelines and clinical care [3–5]. Nevertheless, with the aging of the population and rising disease prevalence, interest in the development of newer approaches has continued, and several are now under investigation [6, 7]. The need for novel paradigms is further highlighted by the fact that intensification of antagonism of the RAAS has not been shown to reduce mortality [8–10], and other pharmacologic and device approaches including anticytokine therapy, epicardial constraining devices, and novel stimulation technologies have not been convincingly associated with improvements in hard clinical outcomes [11–13]. There are also multiple clinical scenarios that suggest areas of unmet need in HF such as CRT non-responders and patients who are not candidates for CRT due to narrow complex QRS morphologies [14, 15]. Thus, there continues to be a need for innovative therapies for patients with heart failure.
One area of recent focus in heart failure research has been the role of autonomic imbalance. In particular, there is increasing evidence that in addition to increased sympathetic activation, parasympathetic withdrawal may also contribute to the pathogenesis of heart failure [16]. However, while beta-blockade has found its place as a leading disease modifying therapy that impacts the sympathetic nervous system, far less is known about methods to augment parasympathetic function. In this context, the topics of vagus nerve anatomy, physiology and influence on cardiac function are reviewed in detail in the current issue of Heart Failure Reviews. These papers form a foundation for understanding the clinical potential of a new intervention, vagus nerve stimulation (VNS). Pre-clinical data (including models of acute ischemia and chronic failure) and phase II experience in Europe with VNS are reviewed as are other potential ways to influence vagus nerve function. The current issue begins with a historical overview of experimental physiologic and clinical-translational work performed by Dr. Peter Schwartz and colleagues, on parasympathetic–sympathetic interactions in both ischemic heart disease and heart failure [17]. Drs. Chapleau and Sabharwal provide a highly detailed review of the concepts of cardiovagal tone, parasympathetic modulation, parasympathetic re-activation, and reflex changes in heart rate and the methods used to assess them [18]. Normal vagus nerve anatomy is described in an elegant paper by Bibevski and Dunlap, who discuss the multitude of potential sites that might contribute to impaired parasympathetic nerve activity and offer evidence that points to specific locations of the defects, including the post-ganglionic nicotinic acetylcholine receptor [19]. The potential mechanisms that mediate the effects of VNS in heart failure are discussed by Li and Olshansky, who review the influence of efferent and
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