The autonomic balance predicts cardiac responses after the first dose of fingolimod

S. Rossi, C. Rocchi, V. Studer, C. Motta, B. Lauretti, G. Germani, G. Macchiarulo, G. A. Marfia, D. Centonze

Research output: Contribution to journalArticlepeer-review


Background: Predictive markers of cardiac side effects would be helpful for the stratification andindividualized monitoring of multiple sclerosis (MS) patients prescribed with fingolimod.Objective: To test whether the autonomic balance predicts a cardiac response after the first dose offingolimod.Methods: A total of 55 consecutive relapsingremitting MS (RRMS) patients underwent head-up tilt,Valsalva maneuver, deep breathing and handgrip tests before their first dose of fingolimod. The normalizedunit of the high frequency (HF) component (HF normalized units; HFnu), reflecting mostly vagalactivity; and the low frequency (LF) component (LF normalized units; LFnu) reflecting mostly sympatheticactivity, were considered for the analysis of heart rate (HR) variability. The patients HR andelectrocardiographic parameters ((the interval between P wave and ventricular depolarization (PR); theinterval between Q and T waves (QT)) were recorded during 6-hour post-dose monitoring.Results: We found significant correlations between measures of parasympathetic function and fingolimod-induced bradycardia. Subjects with higher Valsalva ratio and HR variation during deep breathinghad, in fact, nadir HR ≤50 beats/minute (bpm) after the first fingolimod dose. Conversely, significantnegative correlations were found between measures of sympathetic function and fingolimod-induced PRinterval increase. Subjects with lower LFnu at rest and less increase of blood pressure on the handgrip testshowed a PR interval increase > 20 ms after fingolimod.Conclusions: Assessing autonomic control of cardiovascular functions can be useful to predict cardiaceffects after the first fingolimod dose.

Original languageEnglish
Pages (from-to)206-216
Number of pages11
JournalMultiple Sclerosis Journal
Issue number2
Publication statusPublished - Feb 17 2015


  • Autonomic system
  • Bradycardia
  • Cardiovascular function
  • Fingolimod
  • Heart rate
  • Multiple sclerosis
  • Patient stratification
  • Prediction

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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