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

Abstract

BackgroundPostexercise 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.MethodsA 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).ResultsWith 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).ConclusionUsing 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.

Prognostic Value of NT-Pro Brain Natriuretic Peptide During Exercise Recovery in Ischemic Heart Failure of Reduced, Midrange, and Preserved Ejection Fraction

“…In our previous work, we demonstrated that cardiopulmonary parameters decline more slowly in patients with IHD, indicating that repayment of the O 2 debt is prolonged in these patients in parallel with the delayed recovery of energy stores in skeletal muscle, which had strong prognostic power 25. The HRR-1 was found to have an immense prognostic power in patients with IHD 18–20. Several studies reported prolonged kinetics of V˙ o 2 or V˙ co 2 during recovery from maximal exercise in patients with HF, which was explained by impairment of the circulatory response to exercise and delayed recovery of cardiac output after exercise 24,41.…”

“…25 The HRR-1 was found to have an immense prognostic power in patients with IHD. [18][19][20] Several studies reported prolonged kinetics of V . o 2 or V .…”

“…It is known that IHD and HF are characterized by delayed recovery of energy stores in peripheral muscle, affecting performance of the cardiovascular system 23,24. Previous studies demonstrate that HR declines more slowly during exercise recovery in patients with IHD and HF in comparison to healthy population, portending significant prognostic information 18–21. In our previous work, we have shown that gas analysis during exercise recovery holds diagnostic and prognostic value in patients with IHD 25.…”

“…Exercise induces an increase in NT-pro-BNP in patients with HF and has been shown to be a reliable parameter in predicting a low left ventricular ejection fraction (LVEF) and may help in the identification of patients at high risk for mortality 17. Recently, the importance of the recovery phase after exercise has been reported in patients with IHD and HF 18–21. Previous research demonstrates an increase in cardiac troponin I after exercise due to mild myocardial damage in patients with moderate HF 22.…”