神经调节炎症治疗射血分数保留心力衰竭的疗效：一项初步的随机临床试验。

Background A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction. Low-level transcutaneous vagus nerve stimulation suppresses inflammation in humans. We conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low-level transcutaneous vagus nerve stimulation on cardiac function, exercise capacity, and inflammation in patients with heart failure with preserved ejection fraction. Methods and Results Patients with heart failure with preserved ejection fraction and at least 2 additional comorbidities (obesity, diabetes, hypertension, or age ≥65 years) were randomized to either active (tragus) or sham (earlobe) low-level transcutaneous vagus nerve stimulation (20 Hz, 1 mA below discomfort threshold), for 1 hour daily for 3 months. Echocardiography, 6-minute walk test, quality of life, and serum cytokines were assessed at baseline and 3 months. Fifty-two patients (mean age 70.4±9.2 years; 70% female) were included (active, n=26; sham, n=26). Baseline characteristics were balanced between the 2 arms. Adherence to the protocol of daily stimulation was >90% in both arms (>0.05). While the early mitral inflow Doppler velocity to the early diastolic mitral annulus velocity ratio did not differ between groups, global longitudinal strain and tumor necrosis factor-α levels at 3 months were significantly improved in the active compared with the sham arm (-18.6%±2.5% versus -16.0%±2.4%, =0.002; 8.9±2.8 pg/mL versus 11.3±2.9 pg/mL, =0.007, respectively). The reduction in tumor necrosis factor-α levels correlated with global longitudinal strain improvement (r=-0.73, =0.001). Quality of life was better in the active arm. No device-related side effects were observed. Conclusions Neuromodulation with low-level transcutaneous vagus nerve stimulation over 3 months resulted in a significant improvement in global longitudinal strain, inflammatory cytokines, and quality of life in patients with heart failure with preserved ejection fraction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03327649.

背景：全身性促炎状态在射血分数保留型心力衰竭的发展中起核心作用。低水平经皮迷走神经刺激可抑制人类的炎症反应。我们进行了一项假对照、双盲、随机临床试验，以检验慢性低水平经皮迷走神经刺激对射血分数保留型心力衰竭患者心功能、运动能力和炎症的影响。

方法和结果：射血分数保留型心力衰竭合并至少 2 种合并症（肥胖、糖尿病、高血压或年龄≥65 岁）的患者被随机分配至真刺激（耳屏）或假刺激（耳垂）低水平经皮迷走神经刺激（20Hz，低于不适阈值 1mA），每天 1 小时，持续 3 个月。在基线和 3 个月时评估超声心动图、6 分钟步行试验、生活质量和血清细胞因子。52 例患者（平均年龄 70.4±9.2 岁，70%为女性）纳入研究（真刺激组 26 例，假刺激组 26 例）。两组间基线特征平衡。两组的日常刺激方案的依从性均＞90%（＞0.05）。两组间早期二尖瓣流入多普勒速度与舒张早期二尖瓣环速度比值无差异，但真刺激组较假刺激组的整体纵向应变和肿瘤坏死因子-α水平在 3 个月时显著改善（-18.6%±2.5%比-16.0%±2.4%，=0.002；8.9±2.8pg/mL 比 11.3±2.9pg/mL，=0.007）。肿瘤坏死因子-α水平的降低与整体纵向应变的改善相关（r=-0.73，=0.001）。真刺激组的生活质量更好。未观察到与设备相关的不良反应。

结论：3 个月的低水平经皮迷走神经刺激神经调节可显著改善射血分数保留型心力衰竭患者的整体纵向应变、炎症细胞因子和生活质量。

注册网址：https://www.clinicaltrials.gov；唯一标识符：NCT03327649。