Neural and Spinal Stimulation

Introduction

Heart failure (HF) is a substantial cause of mortality, morbidity, and health care expenditure worldwide. The burden of HF is enormous; up to 5.8 million patients in the USA and over 23 million patients worldwide suffer from HF. The lifetime risk of developing HF is one in five, and it is associated with substantial morbidity and mortality; 5-year mortality rivals that of many cancers. As the risk of HF increases with advancing age, the total number of patients with HF is expected to increase 2 to 3 times because of the ageing global population. The incidence of HF is also increasing as a result of improved treatment and survival following acute myocardial infarction (MI). Despite the current advances in the pharmacologic and device management of patients with systolic HF, the associated mortality remains high. Therefore there is a compelling need for new therapies that target the underlying pathophysiology of HF and further improve clinical outcome.

The heart is regulated by tonic interaction between the sympathetic and parasympathetic arms of the autonomic nervous system (ANS). This interaction plays a critical role in the physiologic and pathophysiologic control of the heart. In HF increased sympathetic tone is observed, and this is associated with progression of HF and increased mortality. Moreover, decreased parasympathetic tone and impaired baroreflex control of sympathetic activity are also observed in HF and are associated with increased mortality. The same occurs among patients with postmyocardial infarction. It is well recognized that these imbalances in ANS activities are associated with the elaboration of different neurohormones (e.g., norepinephrine, angiotensin II, aldosterone), which help to maintain cardiovascular homeostasis through increased volume expansion, peripheral arterial vasoconstriction, and increased myocardial contractility. Unfortunately, high and sustained elevations of these neurohormones are toxic to the heart and circulation and subsequently cause progression of HF and increase mortality. Understanding the pivotal role of these neurohormonal activations in HF progression has resulted in the clinical application of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists, and β-blockers to treat patients with HF caused by reduced left ventricular ejection fraction (LVEF), that is, systolic HF. These agents have been shown to improve mortality and reduce morbidity in patients with systolic HF. Nevertheless, these evidence-based therapies in patients with systolic HF fail to completely restore normal autonomic balance disrupted as a part of HF pathophysiology.

During the last 10 years a concept has progressively developed regarding the possibility that a novel nonpharmacologic approach capable of modulating the ANS and interfering with its detrimental effects may further improve symptoms and/or the clinical outcome in HF. This has led to different approaches of neuromodulation using implantable devices that aim at restoring the sympathovagal imbalance in HF. Similarly, the ANS also plays an important role in the modulation of the cardiac electrophysiology and arrhythmogenesis. Sympathetic activation facilitates ventricular arrhythmias, whereas vagal nerve stimulation (VNS) can reduce or prevent life-threatening ventricular arrhythmias. Therefore device therapies for neuromodulation may also be useful for treatment of cardiac arrhythmias.

In this chapter, we review the experimental basis, rationale, and design of ongoing clinical trials that are focused on the use of VNS, spinal cord stimulation (SCS), and baroreceptor activation for treatment of HF and cardiac arrhythmias ( Fig. 24-1 ).