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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 ( NCT 01823887) 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.

annals of noninvasive electrocardiology

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