title: Effect of fingolimod on cardiac autonomic regulation in patients with multiple sclerosis.
abstract: Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue.
  
  
  
  To investigate the effects of fingolimod on cardiac autonomic regulation prospectively.
  
  
  
  Twenty-seven relapsing-remitting multiple sclerosis patients underwent 24-hour electrocardiogram recording before, at the first day of fingolimod treatment (1d) and after three months of continuous dosing (3mo). The time interval between two consecutive R-peaks (RR-interval) was measured. Cardiac autonomic regulation was assessed by the various parameters of heart rate variability. Parasympathetic stimulation prolongs the RR-interval and increases heart rate variability while the effects of sympathetic stimulation are mainly the opposite. The low frequency/high frequency ratio reflects sympathovagal balance.
  
  
  
  From baseline to 1d, a prolongation of the RR-interval (P<0.001), an increase in the values of various heart rate variability parameters (P<0.05 to P<0.001) and a decrease in the low frequency/high frequency ratio (P<0.05) were demonstrated. At 3mo, although the RR-interval remained longer (P<0.01), the values of various heart rate variability parameters were lower (P<0.01 to P<0.001) as compared to baseline. At 3mo, the low frequency/high frequency ratio (P<0.05) was higher in men than in women although no such difference was found at baseline or at 1d.
  
  
  
  After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men. Careful follow-up of fingolimod-treated relapsing-remitting multiple sclerosis patients is warranted as sympathetic predominance associates generally with impaired outcome.ClinicalTrials.cov: NCT01704183.
authors.affiliation: Department of Neurology, Mikkeli Central Hospital, Finland sakari.simula@esshp.fi.
authors.forename: Sakari
authors.initials: S
authors.lastname: Simula
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Laitinen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Finland.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Laitinen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Mikkeli Central Hospital, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Tarkiainen
authors.affiliation: Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Hartikainen
authors.affiliation: Heart Center, Kuopio University Hospital and University of Eastern Finland, Finland.
authors.forename: Juha Ek
authors.initials: JE
authors.lastname: Hartikainen
mesh_terms: D000328:Adult; D015716:Electrocardiography, Ambulatory; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D011446:Prospective Studies; D012737:Sex Factors; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Cardiac autonomic regulation; fingolimod; heart rate variability; multiple sclerosis