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. 2021 Nov 24:8:766676.
doi: 10.3389/fcvm.2021.766676. eCollection 2021.

Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis

Lucas Bonacossa Sant'Anna  1 , Sérgio Lívio Menezes Couceiro  2 , Eduardo Amar Ferreira  1 , Mariana Bonacossa Sant'Anna  1 , Pedro Rey Cardoso  1 , Evandro Tinoco Mesquita  3 , Guilherme Mendes Sant'Anna  4 , Fernando Mendes Sant'Anna  2   5
Affiliations

Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis

Lucas Bonacossa Sant'Anna et al. Front Cardiovasc Med. .

Abstract

Objectives: The aim of this study was to evaluate the effects of invasive vagal nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). Background: Heart failure is characterized by autonomic nervous system imbalance and electrical events that can lead to sudden death. The effects of parasympathetic (vagal) stimulation in patients with HF are not well-established. Methods: From May 1994 to July 2020, a systematic review was performed using PubMed, Embase, and Cochrane Library for clinical trials, comparing VNS with medical therapy for the management of chronic HFrEF (EF ≤ 40%). A meta-analysis of several outcomes and adverse effects was completed, and GRADE was used to assess the level of evidence. Results: Four randomized controlled trials (RCT) and three prospective studies, totalizing 1,263 patients were identified; 756 treated with VNS and 507 with medical therapy. RCT data were included in the meta-analysis (fixed-effect distribution). Adverse effects related to VNS were observed in only 11% of patients. VNS was associated with significant improvement (GRADE = High) in the New York Heart Association (NYHA) functional class (OR, 2.72, 95% CI: 2.07-3.57, p < 0.0001), quality of life (MD -14.18, 95% CI: -18.09 to -10.28, p < 0.0001), a 6-min walk test (MD, 55.46, 95% CI: 39.11-71.81, p < 0.0001) and NT-proBNP levels (MD -144.25, 95% CI: -238.31 to -50.18, p = 0.003). There was no difference in mortality (OR, 1.24; 95% CI: 0.82-1.89, p = 0.43). Conclusions: A high grade of evidence demonstrated that vagal nerve stimulation improves NYHA functional class, a 6-min walk test, quality of life, and NT-proBNP levels in patients with chronic HFrEF, with no differences in mortality.

Keywords: 6 min walk distance (6 MWD); NYHA class; chronic heart failure; reduced ejection fraction; vagal nerve stimulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Graphical Abstract
Graphical Abstract
Summary of the study.
Figure 1
Figure 1
A study flowchart.
Figure 2
Figure 2
All-cause mortality during follow-up between vagal nerve stimulation and control groups for management of chronic heart failure with reduced ejection fraction. VNS, vagus nerve stimulation.
Figure 3
Figure 3
Improvement of at least one New York Heart Association functional class during follow-up between VNS and control groups for management of chronic heart failure with reduced ejection fraction. VNS, vagus nerve stimulation.
Figure 4
Figure 4
Improvement of quality of life during follow-up between VNS and control groups for management of chronic heart failure with reduced ejection fraction. VNS, vagus nerve stimulation.
Figure 5
Figure 5
Improvement of the 6-min walking test during follow-up between VNS and control groups for management of chronic heart failure with reduced ejection fraction. VNS, vagus nerve stimulation.
Figure 6
Figure 6
Improvement of NT-proBNP levels during follow-up between VNS and control groups for management of chronic heart failure with reduced ejection fraction. VNS, vagus nerve stimulation.
See this image and copyright information in PMC

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