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. 2017 Sep;22(5):e12436.
doi: 10.1111/anec.12436. Epub 2017 Feb 17.

Novel method to assess intrinsic heart rate recovery in ambulatory ECG recordings tracks cardioprotective effects of chronic autonomic regulation therapy in patients enrolled in the ANTHEM-HF study

Gerrard M Carlson  1 , Imad Libbus  1 , Badri Amurthur  1 , Bruce H KenKnight  1 , Richard L Verrier  2
Affiliations

Novel method to assess intrinsic heart rate recovery in ambulatory ECG recordings tracks cardioprotective effects of chronic autonomic regulation therapy in patients enrolled in the ANTHEM-HF study

Gerrard M Carlson et al. Ann Noninvasive Electrocardiol. 2017 Sep.

Abstract

Background: Postexercise heart rate recovery (HRR) is a powerful and independent predictor of mortality. Autonomic regulation therapy (ART) with chronic vagus nerve stimulation (VNS) has been shown to improve ventricular function in patients with chronic heart failure. However, the effect of ART on HRR in patients with heart failure remains unknown.

Methods: A new measure involving quantification of intrinsic HRR was developed for 24-hr ambulatory ECG (AECG) recordings based on spontaneous heart rate changes observed during daily activity in patients with symptomatic heart failure and reduced ejection fraction. Intrinsic HRR values were compared in 21 patients enrolled in the ANTHEM-HF study (NCT01823887) before and after 12 months of chronic ART (10 Hz, 250 μs pulse width, 18% duty cycle, maximum tolerable current amplitude after 10 weeks of titration) and to values from normal subjects (PhysioNet database, n = 54).

Results: With chronic ART, average intrinsic HRR was improved as indicated by a shortening of the rate-recovery time constant by 8.9% (from 12.3 ± 0.1 at baseline to 11.2 ± 0.1 s, p < .0001) among patients receiving high-intensity stimuli (≥2 mA). In addition, mean heart rate decreased by 8.5 bpm (from 75.9 ± 2.6 to 67.4 ± 2.9 bpm, p = .005) and left ventricular ejection fraction (LVEF) increased by 4.7% (from 32.6 ± 2.0% to 37.3 ± 1.9%, p < .005).

Conclusion: Using a new technique adapted for 24-hr AECG recordings, intrinsic HRR was found to be impaired in patients with symptomatic HF compared to normal subjects. Chronic ART significantly improved intrinsic HRR, indicating an improvement in autonomic function.

Keywords: autonomic reflexes; autonomic regulation therapy; baroreflex sensitivity; heart failure; heart rate recovery; vagus nerve stimulation.

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Figures

Figure 1
Figure 1
Method for calculating intrinsic heart rate recovery (HRR) from spontaneous heart rate changes in ambulatory electrocardiograms (AECGs) recorded during daily activity. An initial heart rate maximum point (HR 0) is identified and subsequent HRR to the final heart rate (HR asym) is fit to a mono‐exponential decay with time constant of recovery (TR), based on a sequence of smoothed and decaying heart rate maxima and minima
Figure 2
Figure 2
Gray‐level intrinsic heart rate recovery (HRR) histogram of time constant of recovery (TR), showing the distribution of heart rate‐dependent intrinsic HRR for all qualified intrinsic HRR events for a sample subject. The mean banded relaxation parameter is calculated for each change in heart rate in 1‐bpm increments
Figure 3
Figure 3
Intrinsic heart rate recovery (HRR) (y‐axis) as a function of heart rate change (x‐axis) for normal subjects (solid line) and in patients with heart failure at baseline (dashed line) and after 12 months of chronic autonomic regulation therapy (ART) (dotted line). Patients with low‐intensity stimulation (upper panel) showed no change in intrinsic HRR. Patients with high‐intensity stimulation (lower panel) showed a significant improvement in intrinsic HRR at every change in heart rate (*p < .05; **p < .005)
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