Chronic vagus nerve stimulation is associated with multi-year improvement in intrinsic heart rate recovery and left ventricular ejection fraction in ANTHEM-HF

Figures

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  Fig. 1. Comparison of the pattern of intrinsic heart rate recovery (HRR) based on spontaneous heart rate changes in ambulatory electrocardiograms (AECGs). Essentially, an initial heart rate (HR) maximum point (HRpeak) is identified, and subsequent HRR to the final heart rate (HRtrough) is fit to a mono-exponential decay with time constant of recovery (tau), based on a sequence of smoothed and decaying heart rate maxima and minima, as described in detail in the methods section. The x-axis represents a portion of the 24 h monitoring period, and the y-axis displays the patient’s heart rate. In a representative patient, VNS reduced tau by 40.6%, from 18.0 s at screening (upper panel) to 10.7 s at 36 months of therapy (lower panel)

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  Fig. 2. Intrinsic heart rate recovery (HRR) was calculated based on the mean banded relaxation parameter (y-axis) for several heart rate changes (x-axis) among normal subjects (solid line) and in patients with heart failure at screening (blue line) and after 12 (gold line), 24 (red line), and 36 months (gray line) of vagus nerve stimulation (VNS). Patients with high-intensity VNS (upper panel) showed significant improvements at every change in heart rate compared to screening (*p < 0.05; **p < 0.01), but those with low-intensity VNS (lower panel) showed changes in intrinsic HRR at only a few measurement points

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  Fig. 3. Box-plot comparison by quartiles of heart rate change in response to vagus nerve stimulation in ischemic (n = 15, filled red box) and nonischemic heart failure patients (n = 6, open box) from enrollment to 36 months. The horizontal bar represents the median. The upper and lower sides of the box represent the upper 75th and lower 25th percentiles, respectively, and the whiskers represent the highest and lowest values. Differences in the distribution of values are not statistically significant (p = 0.702)

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  Fig. 4. Inverse correlation between mean banded relaxation parameter and heart rate turbulence (HRT) slope. Both at screening (upper panel) and after 36 months of high-intensity vagus nerve stimulation (VNS) (lower panel), there was an inverse correlation between these two parameters, with r values of 0.67 (p < 0.002) and 0.78 (p < 0.005), respectively. These results suggest that acceleration of heart rate recovery (HRR) is linked to increases in HRT slope, consistent with a baroreceptor-mediated modulation of the spontaneous heart rate response to daily activity