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 of 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.

慢性交感神经系统 (SNS) 过度活跃是心力衰竭 (HF) 与射血分数降低 (HFrEF) 的特征，与预后不良相关并导致死亡风险增加。Sacubitril-valsartan 是一种最近获批的一流血管紧张素受体脑啡肽酶抑制剂 (ARNI) 药物，可显着降低 HFrEF 患者因心血管原因死亡和心衰住院的风险，但这些益处背后的生理机制尚不明确完全理解。这项单臂、开放标签、前瞻性研究旨在检验沙库巴曲缬沙坦短期治疗可降低 HFrEF 患者 SNS 活动的假设，该活动直接通过肌肉交感神经活动 (MSNA) 测量。MSNA，心率（HR），n  = 9, 69 ± 8 岁；28.6 ± 3.6 kg/m ² ) 的现代指导性药物治疗，随后开始服用沙库巴曲缬沙坦。在用沙库巴曲缬沙坦治疗两个月后重复这些测量。Sacubitril-valsartan 降低 MSNA 突发频率（基线：43 ± 10 突发/分钟；2 个月：36 ± 10 突发/分钟，p  = 0.05）和突发发生率（基线：68 ± 16 突发/100 次心跳；2 个月： 55 ± 16 次/100 次心跳，p  = 0.02），而 HR 和 BP 在治疗后没有变化（p > 0.05)。这些初步研究结果为沙库巴曲缬沙坦快速降低 HFrEF 患者 SNS 活性的能力提供了新证据，表明这种新药物类别存在新的交感神经抑制作用。