Ahmed Mohammad, Nudy Matthew, Bussa Rahul, Weigel Frank, Naccarelli Gerald, Maheshwari Ankit
Department of Internal Medicine, Penn State Hershey Medical Center, Hershey, PA 17033, United States of America.
Division of Cardiology, Penn State Hershey Medical Center, Heart and Vascular Institute, Hershey, PA 17033, United States of America.
Trends Cardiovasc Med. 2024 Feb;34(2):101-107. doi: 10.1016/j.tcm.2022.09.007. Epub 2022 Oct 4.
Treatment strategies that modulate autonomic tone through interventional and device-based therapies have been studied as an adjunct to pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). The main objective of this study was to perform a meta-analysis of randomized controlled trials which evaluated the efficacy of device-based autonomic modulation for treatment of HFrEF. All randomized-controlled trials testing autonomic neuromodulation device therapy in HFrEF were included in this trial-level analysis. Autonomic neuromodulation techniques included vagal nerve stimulation (VNS), baroreflex activation (BRA), spinal cord stimulator (SCS), and renal denervation (RD). The prespecified primary endpoints included mean change and 95% confidence intervals (CI) of left ventricular ejection fraction (LVEF), NT pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QOL) measures including 6-minute hall walk distance (6-MHWD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ). New York Heart Association (NYHA) functional class improvement was reported as odds ratios and 95% CI of improvement by at least 1 functional class. Eight studies were identified that included 1037 participants (2 VNS, 2 BRA, 1 SCS, and 3 RD trials). This included 6 open-label, 1 single-blind, and 1 sham-controlled, double-blind study. The mean age (±SD) was 61 (±9.3) years. The mean follow-up time was 7.9 months. Twenty percent of the total patients were female, and the mean BMI (±SD) was 29.86 (±4.12). Autonomic neuromodulation device therapy showed a statistically significant improvement in LVEF (4.02%; 95% CI 0.24,7.79), NT-proBNP (-219.80 pg/ml; 95% CI -386.56, -53.03), NYHA functional class (OR 2.32; 95% CI 1.76, 3.07), 6-MHWD (48.39 m; 95% CI 35.49, 61.30), and MLHFQ (-12.20; 95% CI -19.24, -5.16) compared to control. In patients with HFrEF, the use of autonomic neuromodulation device therapy is associated with improvement in LVEF, reduction in NT-proBNP, and improvement in patient-centered QOL outcomes in mostly small open-label trials. Large, double-blind, sham-controlled trials designed to detect differences in hard cardiovascular outcomes are needed before widespread use and adoption of autonomic neuromodulation device therapies in HFrEF.
通过介入性和基于设备的疗法来调节自主神经张力的治疗策略，已作为射血分数降低的心力衰竭（HFrEF）药物治疗的辅助手段进行了研究。本研究的主要目的是对评估基于设备的自主神经调节治疗HFrEF疗效的随机对照试验进行荟萃分析。所有在HFrEF中测试自主神经调节设备疗法的随机对照试验都纳入了本试验水平分析。自主神经调节技术包括迷走神经刺激（VNS）、压力反射激活（BRA）、脊髓刺激器（SCS）和肾去神经支配（RD）。预先设定的主要终点包括左心室射血分数（LVEF）、N末端B型利钠肽原（NT-proBNP）的平均变化及95%置信区间（CI），以及生活质量（QOL）指标，包括6分钟步行距离（6-MHWD）和明尼苏达心力衰竭生活问卷（MLHFQ）。纽约心脏协会（NYHA）功能分级改善情况报告为改善至少1个功能分级的优势比及95%CI。共纳入8项研究，包括1037名参与者（2项VNS、2项BRA、1项SCS和3项RD试验）。其中包括6项开放标签试验、1项单盲试验和1项假对照双盲试验。平均年龄（±标准差）为61（±9.3）岁。平均随访时间为7.9个月。患者总数的20%为女性，平均体重指数（±标准差）为29.86（±4.12）。与对照组相比，自主神经调节设备疗法在LVEF（4.02%；95%CI 0.24，7.79）、NT-proBNP（-219.80 pg/ml；95%CI -386.56，-53.03）、NYHA功能分级（OR 2.32；95%CI 1.76，3.07）、6-MHWD（48.39 m；95%CI 35.49，61.30）和MLHFQ（-12.20；95%CI -19.24，-5.16）方面显示出统计学上的显著改善。在HFrEF患者中，自主神经调节设备疗法的使用与LVEF改善、NT-proBNP降低以及以患者为中心的QOL结局改善相关，这些大多是小型开放标签试验。在HFrEF中广泛使用和采用自主神经调节设备疗法之前，需要进行大规模、双盲、假对照试验以检测硬心血管结局的差异。
