Abstract
Chronic sympathetic nervous system (SNS) overactivity, characteristic of heart failure
(HF) with reduced ejection fraction (HFrEF), is associated with poor prognosis and
contributes to increased mortality risk. Sacubitril-valsartan is a recently approved,
first-in-class, angiotensin receptor neprilysin inhibitor (ARNI) drug that markedly
reduces the risks of death from cardiovascular causes and hospitalization for HF in
patients with HFrEF, but the physiological mechanisms underlying these benefits are
not fully understood. This single-arm, open-label, prospective study sought to test
the hypothesis that short-term treatment with sacubitril-valsartan reduces SNS activity,
measured directly via muscle sympathetic nerve activity (MSNA), in patients with HFrEF.
MSNA, heart rate (HR), and arterial blood pressure (BP) were assessed in stable Class
II and III patients with HFrEF (n = 9, 69 ± 8 yrs.; 28.6 ± 3.6 kg/m2) on contemporary, guideline-directed medical treatment who were subsequently started
on sacubitril-valsartan. These measurements were repeated after two months of treatment
with sacubitril-valsartan. Sacubitril-valsartan reduced MSNA burst frequency (baseline:
43 ± 10 bursts/min; 2-month: 36 ± 10 bursts/min, p = 0.05) and burst incidence (baseline: 68 ± 16 bursts/100 heartbeats; 2-month: 55 ± 16
bursts/100 heartbeats, p = 0.02), while HR and BP were unchanged following the treatment (p > 0.05). These preliminary findings provide new evidence regarding the ability of
sacubitril-valsartan to rapidly reduce SNS activity in patients with HFrEF, suggesting
the presence of a novel sympathoinhibitory effect of this new drug class.
Keywords
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Article info
Publication history
Published online: June 23, 2021
Accepted:
June 13,
2021
Received in revised form:
May 7,
2021
Received:
January 21,
2021
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.
