title: Tp-Te interval predicts heart rate reduction after fingolimod administration in patients with multiple sclerosis.
abstract: BACKGROUND
  FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod.
  
  
  METHODS
  We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration. At these time intervals, conventional and new ECG indexes for cardiac damage, including Tp-Te interval, were measured. Univariate and multivariate analyses were performed to test the outcome of HR reduction more than median difference between baseline and final observations.
  
  
  RESULTS
  69 outpatients with MS (46 males, age 35.1±9.4years, BP 119.0±12.7/73.0±9.3mmHg, HR 73.5±11.4bpm) were included. No relevant adverse reactions were reported. Fingolimod induced progressive systolic (P=0.024) and diastolic (P<0.001) BP, as well as HR (P<0.001) reductions compared to baseline. Prolonged PQ (150.4±19.5 vs. 157.0±19.5ms; P<0.001), QT (374.9±27.0 vs. 400.0±25.8ms; P<0.001), Tp-Te (1.8±0.3 vs. 1.9±0.3mm; P=0.021), and reduced QTc (414.4±24.4 vs. 404.5±24.5ms; P<0.001) intervals were also recorded at final observation. Baseline HR, QT and Tp-Te intervals provided prognostic information at univariate analysis, although Tp-Te interval resulted the best independent predictor for HR reduction at multivariate analysis [0.057 (0.005-0.660); P=0.022].
  
  
  CONCLUSIONS
  This study firstly demonstrates that prolonged Tp-Te interval may identify those MS patients treated with fingolimod at higher risk of having significant, asymptomatic HR reduction during clinical observation.
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy; IRCCS Neuromed, Pozzilli, IS, Italy. Electronic address: giuliano.tocci@uniroma1.it.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tocci
authors.affiliation: Division of Neurology, Department of Neuroscience, Mental Health and Sensitive Organs, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Canichella
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Timpano
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Vivianne
authors.initials: V
authors.lastname: Presta
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Francia
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Musumeci
authors.affiliation: Division of Neurology, Department of Neuroscience, Mental Health and Sensitive Organs, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Fubelli
authors.affiliation: Division of Neurology, Department of Neuroscience, Mental Health and Sensitive Organs, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy; IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.affiliation: Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrucci
mesh_terms: D000328:Adult; D004562:Electrocardiography / Q000187:drug effects* / Q000639:trends; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology*; D010343:Patient Admission / Q000639:trends; D011237:Predictive Value of Tests
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: Blood pressure; Electrocardiogram; Fingolimod; Heart rate; Tp–Te interval