Oscillatory Pattern of Sympathetic Nerve Bursts Is Associated With Baroreflex Function in Heart Failure Patients With Reduced Ejection Fraction

Edgar Toschi-Dias; Nicola Montano; Eleonora Tobaldini; Patrícia F Trevizan; Raphaela V Groehs; Ligia M Antunes-Correa; Thais S Nobre; Denise M Lobo; Allan R K Sales; Linda M Ueno-Pardi; Luciana D N J de Matos; Patrícia A Oliveira; Ana Maria F W Braga; Maria Janieire N N Alves; Carlos E Negrão; Maria Urbana P B Rondon

doi:10.3389/fnins.2021.669535

Oscillatory Pattern of Sympathetic Nerve Bursts Is Associated With Baroreflex Function in Heart Failure Patients With Reduced Ejection Fraction

Front Neurosci. 2021 Aug 31:15:669535. doi: 10.3389/fnins.2021.669535. eCollection 2021.

Authors

Edgar Toschi-Dias^{1

2

3}, Nicola Montano^{2

3}, Eleonora Tobaldini^{2

3}, Patrícia F Trevizan¹, Raphaela V Groehs¹, Ligia M Antunes-Correa¹, Thais S Nobre¹, Denise M Lobo¹, Allan R K Sales¹, Linda M Ueno-Pardi¹, Luciana D N J de Matos¹, Patrícia A Oliveira¹, Ana Maria F W Braga¹, Maria Janieire N N Alves¹, Carlos E Negrão^{1

4}, Maria Urbana P B Rondon⁴

Affiliations

¹ Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
² Department of Internal Medicine, Fondazione IRCSS Ca' Granda, Ospedale Maggiore Policlínico, Milan, Italy.
³ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
⁴ School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.

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 (LF_MSNA/HF_MSNA) 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 LF_MSNA/HF_MSNA index: (1) Lower LF_MSNA/HF_MSNA (lower terciles, n = 46, aged 53 ± 1 y) and (2) Higher LF_MSNA/HF_MSNA (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 LF_MSNA/HF_MSNA, 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 LF_MSNA/HF_MSNA 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 LF_MSNA/HF_MSNA. Further analysis showed an association between the LF_MSNA/HF_MSNA 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 LF_MSNA/HF_MSNA 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 LF_MSNA/HF_MSNA.

Keywords: baroreflex control; cardiovascular variabilities; heart failure; oscillatory pattern; sympathetic nervous system.