Heart failure with reduced ejection fraction (HFrEF) represents a significant public health burden associated with incremental health
care costs. Given the limitations associated with pharmacological autonomic regulation therapy (ART), device-based autonomic
neuromodulation is on the horizon now for ART in those patients. This systematic review aimed primarily to determine the effect of
ART by devices on functional status and quality of life (QOL) in patients with HFrEF. We performed a meta-analysis of five
randomized controlled trials (1074 patients) comparing ART by devices versus optimal medical therapy (OMT) in HFrEF. We
assessed pooled estimates of odds ratio (OR) for improvement in New York Heart Association (NYHA) class and mean differences
(MD) in 6-minute hall walk distance (6-MHWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal
pro b-type natriuretic peptide (NT-proBNP) levels, and left ventricular end-systolic volume index (LVESVi) with their 95% confidence
intervals (CIs) at 6-month follow-up. Compared toOMTalone,ART by devices inHFrEF significantly improvesNYHA class
(OR 2.26, 95% CI 1.33 to 3.83, P = 0.003), increases 6-MHWD (MD 45.53 m, 95% CI 30.61 to 60.45, P < 0.00001), improves
MLHFQ score (MD − 10.59, 95%CI − 20.62 to − 0.57, P = 0.04) with neutral effect onNT-proBNP levels (MD − 236.5 pg/ml, 95%
CI − 523.86 to 50.87, P = 0.11) and LVESVi (MD− 1.01 ml/m2, 95%CI − 4.49 to 2.47, P = 0.57).We concluded that device-based
neuromodulation therapy significantly improves functional status and quality of life in patients with HFrEF.