Abstract

Sympathetic hyperactivation and baroreflex dysfunction are hallmarks of heart failure with reduced ejection fraction (HFrEF). However, it is unknown whether the progressive loss of phasic activity of sympathetic nerve bursts is associated with baroreflex dysfunction in HFrEF patients. Therefore, we investigated the association between the oscillatory pattern of muscle sympathetic nerve activity (LFMSNA/HFMSNA) and the gain and coupling of the sympathetic baroreflex function in HFrEF patients. In a sample of 139 HFrEF patients, two groups were selected according to the level of LFMSNA/HFMSNA index: (1) Lower LFMSNA/HFMSNA (lower terciles, n = 46, aged 53 ± 1 y) and (2) Higher LFMSNA/HFMSNA (upper terciles, n = 47, aged 52 ± 2 y). Heart rate (ECG), arterial pressure (oscillometric method), and muscle sympathetic nerve activity (microneurography) were recorded for 10 min in patients while resting. Spectral analysis of muscle sympathetic nerve activity was conducted to assess the LFMSNA/HFMSNA, and cross-spectral analysis between diastolic arterial pressure, and muscle sympathetic nerve activity was conducted to assess the sympathetic baroreflex function. HFrEF patients with lower LFMSNA/HFMSNA had reduced left ventricular ejection fraction (26 ± 1 vs. 29 ± 1%, P = 0.03), gain (0.15 ± 0.03 vs. 0.30 ± 0.04 a.u./mmHg, P < 0.001) and coupling of sympathetic baroreflex function (0.26 ± 0.03 vs. 0.56 ± 0.04%, P < 0.001) and increased muscle sympathetic nerve activity (48 ± 2 vs. 41 ± 2 bursts/min, P < 0.01) and heart rate (71 ± 2 vs. 61 ± 2 bpm, P < 0.001) compared with HFrEF patients with higher LFMSNA/HFMSNA. Further analysis showed an association between the LFMSNA/HFMSNA with coupling of sympathetic baroreflex function (R = 0.56, P < 0.001) and left ventricular ejection fraction (R = 0.23, P = 0.02). In conclusion, there is a direct association between LFMSNA/HFMSNA and sympathetic baroreflex function and muscle sympathetic nerve activity in HFrEF patients. This finding has clinical implications, because left ventricular ejection fraction is less in the HFrEF patients with lower LFMSNA/HFMSNA.

Highlights

  • Heart failure is a complex syndrome and considered the leading cause of hospitalization in patients over the age of 60 years, which accounts for about 30–40% of the mortality of these patients (Ponikowski et al, 2016)

  • left ventricular ejection fraction (LVEF) and VO2 were significantly lower and HR and proportion of patients using anticoagulant were significantly higher in the group with lower LFMSNA/HFMSNA compared with the group with higher LFMSNA/HFMSNA

  • The loss of the physiological autonomic modulatory pattern characterized by a paradoxical decrease of LF component in the lower LFMSNA/HFMSNA group was observed in the R-R interval (RRi), systolic arterial pressure (SAP), and DAP variability

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Summary

Introduction

Heart failure is a complex syndrome and considered the leading cause of hospitalization in patients over the age of 60 years, which accounts for about 30–40% of the mortality of these patients (Ponikowski et al, 2016). It is known that the sympathetic nervous system influence on cardiovascular control depends on its tonic and its phasic activity (i.e., modulation) Both the frequency and the intensity of the sympathetic nerve discharge determine a pattern of oscillation that influences the efficiency of sympathetic effector response (Toschi-Dias et al, 2013). This modulation of sympathetic nerve bursts may be evaluated by the balance between the spectral components of low (LF) and high frequency (HF) sympathetic nerve activity and represents the intrinsic behavior of sympathetic nervous system functioning (van de Borne et al, 1997; Toschi-Dias et al, 2013)

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