title: The autonomic balance predicts cardiac responses after the first dose of fingolimod.
abstract: BACKGROUND
  Predictive markers of cardiac side effects would be helpful for the stratification and individualized monitoring of multiple sclerosis (MS) patients prescribed with fingolimod.
  
  
  OBJECTIVE
  To test whether the autonomic balance predicts a cardiac response after the first dose of fingolimod.
  
  
  METHODS
  A total of 55 consecutive relapsing-remitting MS (RRMS) patients underwent 'head-up tilt', Valsalva maneuver, deep breathing and handgrip tests before their first dose of fingolimod. The normalized unit of the high frequency (HF) component (HF normalized units; HFnu), reflecting mostly vagal activity; and the low frequency (LF) component (LF normalized units; LFnu) reflecting mostly sympathetic activity, were considered for the analysis of heart rate (HR) variability. The patients' HR and electrocardiographic parameters ((the interval between P wave and ventricular depolarization (PR); the interval 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 breathing had, in fact, nadir HR ≤ 50 beats/minute (bpm) after the first fingolimod dose. Conversely, significant negative correlations were found between measures of sympathetic function and fingolimod-induced PR interval increase. Subjects with lower LFnu at rest and less increase of blood pressure on the handgrip test showed a PR interval increase > 20 ms after fingolimod.
  
  
  CONCLUSIONS
  Assessing autonomic control of cardiovascular functions can be useful to predict cardiac effects after the first fingolimod dose.
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), Rome, Italy.
authors: S
authors: S
authors: Rossi
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy.
authors: C
authors: C
authors: Rocchi
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), Rome, Italy.
authors: V
authors: V
authors: Studer
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), Rome, Italy.
authors: C
authors: C
authors: Motta
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy.
authors: B
authors: B
authors: Lauretti
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), Rome, Italy.
authors: G
authors: G
authors: Germani
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), Rome, Italy.
authors: G
authors: G
authors: Macchiarulo
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy.
authors: G A
authors: GA
authors: Marfia
authors: Clinica Neurologica, Università Tor Vergata, Rome, Italy/Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), Rome, Italy centonze@uniroma2.it.
authors: D
authors: D
authors: Centonze
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects*; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Autonomic system; bradycardia; cardiovascular function; fingolimod; heart rate; multiple sclerosis; patient stratification; prediction