Dataset Information

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

ABSTRACT:

Background

In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions.

Objectives

To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation.

Methods

Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing-up, during metronomic deep-breathing, Valsalva-maneuver, and "sustained-handgrip-exercise" in 21 patients with relapsing-remitting MS, and 20 healthy persons. We calculated sympathetic and parasympathetic cardiovascular parameters, including low- (LF) and high-frequency (HF) powers of RRI- and BP-oscillations, RRI-RMSSDs, RRI- and BP-changes during handgrip-exercise, parasympathetic heart-rate-slowing in relation to BP-overshoot after Valsalva-strain-release. We compared values of healthy persons and patients with and without prolonged heart-rate slowing after Fingolimod-initiation (ANOVA; significance: p<0.05).

Results

Upon Fingolimod-initiation, 7/21 patients had prolonged HR-slowing. Before Fingolimod, these patients had higher resting BP and higher BP increase during handgrip-exercise than had the other participants (p<0.05). They did not reduce parasympathetic HR-parameters upon standing-up. After Valsalva-strain-release, their parasympathetic HR-slowing in response to BP-overshoot was four times higher than in the other participants (p<0.05).

Conclusions

The autonomic cardiovascular dysfunction in MS-patients with delayed HR-re-acceleration upon Fingolimod-initiation suggests that MS-related central autonomic lesions compromise HR-re-acceleration upon Fingolimod.

Trial registration

German Clinical Trial Register DRKS00004548 http://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do.

SUBMITTER: Hilz MJ

PROVIDER: S-EPMC4493029 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

Hilz Max J MJ Intravooth Tassanai T Moeller Sebastian S Wang Ruihao R Lee De-Hyung DH Koehn Julia J Linker Ralf A RA

PloS one 20150706 7

<h4>Background</h4>In multiple sclerosis (MS) patients, Fingolimod may induce prolonged heart-rate slowing which might be caused by MS-related central autonomic lesions.<h4>Objectives</h4>To evaluate whether MS-patients with prolonged heart-rate slowing (> six hours) upon Fingolimod show cardiovascular-autonomic dysfunction before Fingolimod-initiation.<h4>Methods</h4>Before Fingolimod-initiation, we recorded electrocardiographic RR-intervals (RRIs) and blood-pressure (BP) at rest, upon standing ...[more]

PMID: 26147106

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Project description:Type 1 diabetes mellitus (T1DM) has an important impact on morbidity and mortality because it may start early in life. Therefore, the early detection of cardiovascular autonomic neuropathy (DCAN) in T1DM patients is important to intervene quickly and prevent further deterioration. Traditional autonomic function tests detect abnormalities in severely symptomatic patients but they are difficult to be standardized, require the patient’s active participation and their sensitivity to the early disease is limited. In comparison, heart rate variability (HRV) is easier to be measured and standardized. Therefore, we aim to find the HRV indexes that better identify DCAN at an early stage in T1DM patients, and evaluate if HRV is a valid alternative to traditional tests. For this aim, we administered the SCOPA-AUT questionnaire on symptoms of autonomic dysfunction as well as deep breathing, Valsalva, handgrip, head-up tilt (HUT), and cold-pressor tests, to 52 T1DM patients and 27 controls. We calculated HRV indexes during supine rest (SUP) and HUT, assessing differences between groups and postures by a linear mixed-effect model for repeated measures. Receiver Operating Characteristic (ROC) analysis quantified how each HRV index and autonomic test distinguishes between patients and controls. We found that the SCOPA-AUT score was slightly but significantly (p < 0.05) greater in patients, indicating an early DCAN. T1DM patients preserved the HRV response to changing posture but in SUP they showed significantly lower standard deviation and vagal indexes of HRV than controls. The area under the ROC curve of these HRV indexes was not lower than 0.68. By contrast, traditional autonomic tests did not differ between groups. Therefore, early DCAN initially causes an impairment of the cardiac vagal control manifest in conditions of elevated vagal tone, as in SUP. Compensatory adjustments of the sympathetic control might explain the unaltered response to traditional autonomic tests. In conclusion, vagal HRV indexes in SUP help to identify early DCAN better than traditional tests, potentially allowing rapid interventions.

Dataset Information

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

Background

Objectives

Methods

Results

Conclusions

Trial registration

Publications

Central Autonomic Dysfunction Delays Recovery of Fingolimod Induced Heart Rate Slowing.

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