Li Kai, Konofalska Urszula, Akgün Katja, Reimann Manja, Rüdiger Heinz, Haase Rocco, Ziemssen Tjalf
Autonomic and Neuroendocrinological Lab, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.
Department of Neurology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Front Neurosci. 2017 Oct 12;11:540. doi: 10.3389/fnins.2017.00540. eCollection 2017.
It is well-known that initiation of fingolimod induces a transient decrease of heart rate. However, the underlying cardiac autonomic regulation is poorly understood. We aimed to investigate the changes of autonomic activity caused by the first dose of fingolimod using a long-term multiple trigonometric spectral analysis for the first time. In addition, we sought to use the continuous Holter ECG recording to find predictors for fingolimod induced bradycardia. Seventy-eight patients with relapsing-remitting multiple sclerosis (RRMS) were included. As a part of the START study (NCT01585298), continuous electrocardiogram was recorded before fingolimod initiation, and until no <6 h post medication. Time domain and frequency domain heart rate variability (HRV) parameters were computed hourly to assess cardiac autonomic regulation. A long-term multiple trigonometric regressive spectral (MTRS) analysis was applied on successive 1-h-length electrocardiogram recordings. Decision tree analysis was used to find predictors for bradycardia following fingolimod initiation. Most of the HRV parameters representing parasympathetic activities began to increase since the second hour after fingolimod administration. These changes of autonomic regulations were in accordance with the decline of heart rate. Baseline heart rate was highly correlated with nadir heart rate, and was the only significant predicting factor for fingolimod induced bradycardia among various demographic, clinical and cardiovascular variables in the decision tree analysis. The first dose application of fingolimod enhances the cardiac parasympathetic activity during the first 6 h post medication, which might be the underlying autonomic mechanism of reduced heart rate. Baseline heart rate is a powerful predictor for bradycardia caused by fingolimod.
众所周知，芬戈莫德的起始治疗会导致心率短暂下降。然而，其潜在的心脏自主神经调节机制却知之甚少。我们旨在首次使用长期多重三角谱分析来研究首剂芬戈莫德引起的自主神经活动变化。此外，我们试图通过连续动态心电图记录来寻找芬戈莫德诱发心动过缓的预测因素。纳入了78例复发缓解型多发性硬化症（RRMS）患者。作为START研究（NCT01585298）的一部分，在开始使用芬戈莫德之前以及用药后至少6小时内记录连续心电图。每小时计算时域和频域心率变异性（HRV）参数，以评估心脏自主神经调节。对连续1小时时长的心电图记录应用长期多重三角回归谱（MTRS）分析。使用决策树分析来寻找芬戈莫德起始治疗后心动过缓的预测因素。大多数代表副交感神经活动的HRV参数自芬戈莫德给药后第二小时开始增加。这些自主神经调节的变化与心率下降一致。基线心率与最低心率高度相关，并且在决策树分析中的各种人口统计学、临床和心血管变量中，是芬戈莫德诱发心动过缓的唯一显著预测因素。首剂芬戈莫德在用药后的前6小时增强了心脏副交感神经活动，这可能是心率降低的潜在自主神经机制。基线心率是芬戈莫德引起心动过缓的有力预测因素。
