Department of Neurology, Cantonal Hospital, St. Gallen, Switzerland.
Department of Neurology, Cantonal Hospital, Fribourg, Switzerland.
J Neurol. 2017 Nov;264(11):2313-2317. doi: 10.1007/s00415-017-8636-3. Epub 2017 Oct 9.
The objective is to prospectively investigate short- and mid-term changes of heart rate variability (HRV) in patients with relapsing-remitting multiple sclerosis (RRMS), being started on fingolimod. In this prospective clinical trial, patient (n = 33) with RRMS starting treatment with fingolimod underwent a time-domain-based analysis of HRV (breathing at rest, deep breath, and in response to the Valsalva maneuver) shortly before, 4.5 h and 3 months after first intake. Blood pressure changes after the Valsalva maneuver were used as a marker of the sympathetic noradrenergic system. We used a non-invasive continuous beat-to-beat heart rate and blood pressure monitoring. In addition, the Fatigue Severity Scale and the refined and abbreviated Composite Autonomic Symptom Score were applied. Significant changes in HRV in RRMS patients, following treatment with fingolimod, were detected. After an initial increase in HRV, measured 4.5 h after the first intake of fingolimod, a substantial decrease in HRV occurred within 3 months on continuous treatment. There is a growing body of evidence for short-term cardiovascular side effects in continuous treatment with fingolimod, driven by the ANS. The mechanisms and the clinical relevance of the observed changes in HRV need further evaluation, especially in longer and larger prospective studies.
前瞻性研究复发缓解型多发性硬化症（RRMS）患者在开始使用芬戈莫德后短期和中期心率变异性（HRV）的变化。在这项前瞻性临床试验中，33 名 RRMS 患者在开始使用芬戈莫德治疗前、首次服用后 4.5 小时和 3 个月时进行了基于时域的 HRV（静息呼吸、深呼吸和对瓦尔萨尔瓦动作的反应）分析。在瓦尔萨尔瓦动作后血压的变化被用作交感神经去甲肾上腺素能系统的标志物。我们使用了一种非侵入性的连续心率和血压监测。此外，还应用了疲劳严重程度量表和简化的综合自主症状评分。在 RRMS 患者中，我们检测到治疗后 HRV 的显著变化。在首次服用芬戈莫德后 4.5 小时，HRV 最初增加后，连续治疗 3 个月内 HRV 显著下降。越来越多的证据表明，连续使用芬戈莫德会导致自主神经系统（ANS）出现短期心血管副作用。需要进一步评估观察到的 HRV 变化的机制和临床相关性，特别是在更长和更大的前瞻性研究中。
