Vagal stimulation to suppress alternans: Are we saving lives or simply masking surrogate markers?
Multiple studies have demonstrated that the functional modulation of the heart exerted by the autonomic nervous system (ANS) can prove maladaptive in the context of heart failure (HF), and it is evident that increased sympathetic and reduced parasympathetic tone play an important pathophysiological role in the progression of HF irrespective of its etiology. In light of its implications in the pathogenesis of HF, there has been growing interest in the potential of ANSmodulation as HF therapy. Theoretically, it is conceivable that enhancing parasympathetic tone to counteract the adverse effects of excessive adrenergic activity could ameliorate or even reverse the course of this progressive disease. Parasympathetic modulation of the heart is carried by the right and left vagus nerves, originating in the medulla and connecting with postganglionic neurons in ganglionated plexi located in the epicardium. The anatomical accessibility of the cervical vagus nerves and their response to electrical impulses provide a unique opportunity to interfere with ANS responses to disease. In 1967 Braunwald et al demonstrated that vagal nerve stimulation (VNS) could reproducibly attenuate angina symptoms and improve exercise capacity in 2 patients after myocardial infarction. Schwartz et al studied the effect of VNS in a series of 8 patients with advanced HF. They demonstrated a significant improvement in left ventricular end-systolic volume and functional class. A nonrandomized study of 32 patients with HF with reduced left ventricular ejection fraction (LVEF) reported that VNS favorably influenced quality of life, exercise capacity, and left ventricular remodeling. However, larger randomized studies have failed to systematically replicate these effects. A sham-controlled trial (NECTAR-HF) showed no benefit of VNS in LVEF or left ventricular remodeling. The ANTHEM-HF trial randomly assigned 31 and 29 patients to left and right cervical VNS, respectively. In contrast to NECTAR-HF, modest but