title: Effect of late sodium current inhibition on MRI measured diastolic dysfunction in aortic stenosis: a pilot study.
abstract: BACKGROUND
  Ranolazine is a new anti-anginal drug that acts via late sodium current inhibition, and has been shown to improve diastolic dysfunction in isolated myocytes. Diastolic dysfuntion is common in patients with aortic stenosis (AS), and precedes symptom development and systolic dysfunction. The purpose of this study was to assess the effects of ranolazine on peak early diastolic strain rate (PEDSR) and exercise capacity in patients with AS.
  
  
  METHODS
  Patients with asymptomatic moderate to severe AS and diastolic dysfunction underwent trans-thoracic echocardiography, exercise testing and cardiac magnetic resonance (CMR) imaging at baseline, 6 weeks after commencing ranolazine and at 10 weeks (4 weeks after discontinuation). Diastolic function was assessed using PEDSR measured on tagged CMR images.
  
  
  RESULTS
  Fifteen patients (peak pressure gradient 48.8 ± 12.4 mmHg, mean pressure gradient 27.1 ± 7.5 mmHg, aortic valve area 1.26 ± 0.31 cm(2)) completed the week-6 visit and 13 completed the final visit. Global PEDSR did not significantly increase from baseline (0.79 ± 0.15) to week-6 (0.86 ± 0.18, p = 0.198). There was a borderline significant increase in total exercise duration from 10.47 ± 3.68 min to 11.60 ± 3.25 min (p = 0.06).
  
  
  CONCLUSIONS
  This small pilot study did not show a significant improvement in diastolic function with the use of ranolazine in asymptomatic patients with moderate-severe AS. Further studies with a larger population may be indicated. EduraCT number 2011-000111-26.
authors: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK. as707@le.ac.uk.
authors: Anvesha
authors: A
authors: Singh
authors: Poole Hospital NHS Foundation Trust, Poole, UK. cdsteadman@gmail.com.
authors: Christopher D
authors: CD
authors: Steadman
authors: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK. jk211@le.ac.uk.
authors: Jamal N
authors: JN
authors: Khan
authors: Biostatistics Unit, Medi Service, Genoa, Italy. giorgio.reggiardo@mediservice.it.
authors: Giorgio
authors: G
authors: Reggiardo
authors: Department of Cardiovascular Sciences, University of Leicester and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK. gerry.mccann@uhl-tr.nhs.uk.
authors: Gerry P
authors: GP
authors: McCann
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000503:physiopathology*; D003710:Demography; D003971:Diastole; D023381:Endpoint Determination; D005080:Exercise Test; D006801:Humans; D015640:Ion Channel Gating; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D010865:Pilot Projects; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D015222:Sodium Channels