Multifactorial Benefits of Chronic Vagus Nerve Stimulation on Autonomic Function and Cardiac Electrical Stability in Heart Failure Patients With Reduced Ejection Fraction

Figures

• 

  FIGURE 1. Influence of vagal stimulation in the presence of various levels of adrenergic tone. The vagal effect on ventricular fibrillation threshold (VFT) is demonstrable only when neural or humoral activity is increased (Lown and Verrier, 1976).

• 

  FIGURE 2. Traditional concepts focused on afferent tracts (dashed lines) arising from myocardial nerve terminals and reflex receptors (e.g., baroreceptors) that are integrated centrally within hypothalamic and medullary cardiostimulatory and cardioinhibitory brain centers and on central modulation of sympathetic and parasympathetic outflow (solid lines) with little intermediary processing at the level of the spinal cord and within cervical and thoracic ganglia. More recent views incorporate additional levels of intricate processing within the extraspinal cervical and thoracic ganglia and within the cardiac ganglionic plexus, where interneurons are envisioned to provide levels of non-central integration. Release of neurotransmitters from postganglionic sympathetic neurons is believed to enhance excitation in the sinoatrial node and myocardial cells through norepinephrine binding to β1 receptors, which enhances adenyl cyclase (AC) activity through intermediary stimulatory G proteins (Gs). Increased parasympathetic outflow enhances postganglionic release and binding of acetylcholine to muscarinic (M2) receptors, and through coupled inhibitory G proteins (Gi), inhibits cAMP production. The…

• 

  FIGURE 3. Anatomic organization of the extra-cardiac limbs of the autonomic nervous system (ANS)—the cardio-acceleratory sympathetic and cardio-inhibitory parasympathetic systems. Reprinted with permission from Pearson Education, Inc., from Martini and Nath (2009).

• 

  FIGURE 4. Autonomic regulation therapy (ART) system and approach. Reproduced with permission from LivaNova USA.

• 

  FIGURE 5. Left panel: Time course of effects of vagus nerve stimulation (VNS) therapy on heart rate turbulence (HRT) slope (upper panel), T-wave alternans (TWA) (middle panel), and numbers of patients with non-sustained ventricular tachycardia (NSVT) > 3 beats (lower panel). The increase in HRT slope is associated with the beneficial effect of increasing baroreceptor sensitivity. Mean TWA was reduced from > 70 μV, a severely abnormal level (≥60 μV), to a normal range (<47 μV). The numbers of patients with NSVT were also significantly decreased by chronic VNS therapy. Right panel: TWA recordings from a representative patient at baseline screening and 1 and 3 years after VNS device implantation. Reproduced with permission from Elsevier from Nearing et al. (2021a).

• 

  FIGURE 6. Left panels: Significant improvement in R-wave and T-wave heterogeneity (RWH, TWH) occurred at 6 months following initiation of chronic vagus nerve stimulation (VNS) and persisted throughout the study. Right panel: Substantial, sustained reductions RWH and TWH in a representative study patient. Tracings were obtained at baseline screening and at 6 and 36 months after VNS device implantation. Reproduced with permission from Elsevier from Nearing et al. (2021a).

• 

  FIGURE 7. Effects of chronic vagus nerve stimulation (VNS) therapy on indices of cardiac performance. Significant increases in left ventricular ejection fraction (LVEF) (upper left panel) were observed across the 3-year observation period. A beneficial effect was also observed during the 6-min walk test (6MWT) (upper right panel). All patients exhibited an improvement in New York Heart Association (NYHA) class status (lower panel). By 6 months, NYHA class III patients (filled) were all reclassified to NYHA class I (open) or class II (striped). Reproduced with permission from Elsevier from Nearing et al. (2021a).