title: Heart rate variability predicts the magnitude of heart rate decrease after fingolimod initiation.
abstract: BACKGROUND
  Fingolimod is an immunomodulator with a disease modifying effect on relapsing-remitting multiple sclerosis (RRMS). A heart rate (HR) decrease shortly after fingolimod initiation, however, requires a clinical vigilance. The aim of this study was to prospectively investigate whether cardiac autonomic regulation can predict the magnitude of HR decrease after fingolimod initiation.
  
  
  METHODS
  Twenty-five patients with RRMS underwent ambulatory 24-h electrocardiogram recording to assess HR variability 20±16 days before fingolimod initiation (baseline) and repeated at the day of fingolimod initiation to assess the magnitude of HR decrease. The percentage of normal RR-intervals with duration more than 50ms different from the previous normal RR-interval (pNN50) was calculated (among the other HR variability parameters) to assess cardiac autonomic regulation. The maximal HR decrease (ΔHR) after the first dose of fingolimod was assessed in absolute units (beats/min) and in percentage (%).
  
  
  RESULTS
  The maximal ΔHR was -20±11 beats/min (-23±12%) on the average. pNN50 calculated at baseline correlated with ΔHR% (r=-0.657, p<0.001). A HR decrease ≥20% was found in 10/14 patients with pNN50≥10%. The positive and negative predictive values of pNN50≥10% to predict ΔHR≥20% were 83% and 69%, respectively leading to accuracy of 76%.
  
  
  CONCLUSIONS
  Cardiac autonomic regulation (pNN50>10%) at baseline can be used to predict the magnitude of HR decrease after the first dose of fingolimod.
  
  
  BACKGROUND
  ClinicalTrials.gov (NCT01704183).
authors.affiliation: Department of Neurology, Mikkeli Central Hospital, Mikkeli, Finland. Electronic address: 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, Kuopio, Finland.
authors.forename: Tomi P
authors.initials: TP
authors.lastname: Laitinen
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Laitinen
authors.affiliation: Neuro Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Hartikainen
authors.affiliation: Heart Center Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
authors.forename: Juha Ek
authors.initials: JE
authors.lastname: Hartikainen
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D015716:Electrocardiography, Ambulatory; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D011379:Prognosis
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Fingolimod; Heart rate; Heart rate variability; Multiple sclerosis