Libbus Imad, Premchand Rajendra K, Sharma Kamal, Mittal Sanjay, Monteiro Rufino, Amurthur Badri, KenKnight Bruce H, DiCarlo Lorenzo A, Anand Inder S
LivaNova USA, Inc., Houston, TX, United States.
Krishna Institute of Medical Sciences, Secunderabad, India.
Front Physiol. 2022 Mar 11;13:853617. doi: 10.3389/fphys.2022.853617. eCollection 2022.
Although heart failure (HF) outcomes have improved dramatically with the use of guideline directed medical therapy and implantable devices, the overall prognosis of patients with HF and reduced ejection fraction (HFrEF) remains poor. Autonomic Regulation Therapy (ART) using chronic vagus nerve stimulation (VNS) has been evaluated in the ANTHEM-HF study, using changes in heart rate (HR) dynamics as a biomarker of autonomic nervous system engagement and cardiac control to guide VNS titration. ART was associated with sustained improvement in cardiac function and HF symptoms in patients with HFrEF and persistent HF symptoms despite guideline-directed medical therapy (GDMT). We sought to determine whether the responsiveness of the autonomic nervous system to ART, as reflected in HR response to vagus stimulation during the VNS duty cycle, is maintained after long-term chronic VNS administration.
Fifteen patients with HFrEF and implanted with a VNS systems in the ANTHEM-HF study were evaluated after 4.7 ± 0.3 years (range: 4.0-5.0 years) of chronic ART. ECG electrodes were placed on each patient's wrists, and ECG rhythm strips were recorded. Instantaneous HR time series was computed at each patient's chronically programmed VNS intensity and during progressively increasing VNS intensity. HR during active stimulation (on-time) was compared to HR just prior to initiation of each stimulation cycle (off-time).
Persistent autonomic engagement was observed in a majority of patients (11 of 15, 73%) after chronic ART for four or more years. The average magnitude of HR reduction during ART on-time in all patients was 2.4 ± 3.2 bpm at the chronically programmed VNS pulse parameter settings.
Autonomic responsiveness to VNS persists in patients with HFrEF who received chronic ART for up to 5 years as a supplement to GDMT. This suggests that the effects of ART on autonomic engagement and cardiac control remain durable over time.
[ClinicalTrials.gov], identifier [#NCT01823887, CTRI registration #CTRI/2012/05/002681].
尽管使用指南指导的药物治疗和植入式设备后心力衰竭（HF）的治疗效果有了显著改善，但射血分数降低的心力衰竭（HFrEF）患者的总体预后仍然很差。在ANTHEM-HF研究中，已经对使用慢性迷走神经刺激（VNS）的自主调节疗法（ART）进行了评估，该研究将心率（HR）动态变化作为自主神经系统参与和心脏控制的生物标志物，以指导VNS滴定。对于HFrEF且尽管接受了指南指导的药物治疗（GDMT）仍有持续HF症状的患者，ART与心脏功能和HF症状的持续改善相关。我们试图确定自主神经系统对ART的反应性，即在VNS工作周期中迷走神经刺激的HR反应所反映的反应性，在长期慢性VNS给药后是否得以维持。
在ANTHEM-HF研究中植入VNS系统的15例HFrEF患者在接受4.7±0.3年（范围：4.0 - 5.0年）的慢性ART治疗后进行了评估。将心电图电极放置在每位患者的手腕上，并记录心电图节律条。在每位患者的长期程控VNS强度下以及VNS强度逐渐增加期间计算瞬时HR时间序列。将主动刺激期间（开启时间）的HR与每个刺激周期开始前（关闭时间）的HR进行比较。
在大多数患者（15例中的11例，73%）接受四年或更长时间的慢性ART治疗后，观察到自主神经持续参与。在长期程控的VNS脉冲参数设置下，所有患者在ART开启时间期间HR降低的平均幅度为2.4±3.2次/分钟。
接受长达5年慢性ART作为GDMT补充治疗的HFrEF患者对VNS的自主反应性持续存在。这表明ART对自主神经参与和心脏控制的影响随着时间的推移仍然持久。
[ClinicalTrials.gov]，标识符[#NCT01823887，CTRI注册号CTRI/2012/05/002681]。
