Sakari Simula1, Tomi Laitinen2, Tiina M Laitinen2, Tuula Tarkiainen3, Päivi Hartikainen4, Juha Ek Hartikainen5. 1. Department of Neurology, Mikkeli Central Hospital, Finland sakari.simula@esshp.fi. 2. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Finland. 3. Department of Clinical Physiology and Nuclear Medicine, Mikkeli Central Hospital, Finland. 4. Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Finland. 5. Heart Center, Kuopio University Hospital and University of Eastern Finland, Finland.
Abstract
BACKGROUND: Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue. OBJECTIVE: To investigate the effects of fingolimod on cardiac autonomic regulation prospectively. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND:Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue. OBJECTIVE: To investigate the effects of fingolimod on cardiac autonomic regulation prospectively. METHODS: Twenty-seven relapsing-remitting multiple sclerosispatients 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. RESULTS: 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. CONCLUSIONS: 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 sclerosispatients is warranted as sympathetic predominance associates generally with impaired outcome.ClinicalTrials.cov: NCT01704183.
Authors: Sakari Simula; Tomi P Laitinen; Tiina M Laitinen; Päivi Hartikainen; Juha E K Hartikainen Journal: Ann Noninvasive Electrocardiol Date: 2017-02-13 Impact factor: 1.468
Authors: Jochen Vehoff; Stefan Haegele-Link; Andrea Humm; Georg Kaegi; Stefanie Karin Mueller; Rafael Sauter; Barbara Elisabeth Tettenborn; Thomas Hundsberger Journal: J Neurol Date: 2017-10-09 Impact factor: 4.849
Authors: Bernhard Neumann; Wilhelm Schulte-Mattler; Sophie Brix; Peter Pöschl; Wolfgang Jilg; Ulrich Bogdahn; Andreas Steinbrecher; Ingo Kleiter Journal: Brain Behav Date: 2016-05-05 Impact factor: 2.708
Authors: Aapo Laiho; Tiina M Laitinen; Päivi Hartikainen; Juha E K Hartikainen; Tomi P Laitinen; Sakari Simula Journal: Brain Behav Date: 2018-01-30 Impact factor: 2.708