title: The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations.
abstract: BACKGROUND
  Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation.
  
  
  METHODS
  In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up.
  
  
  RESULTS
  Changes in biventricular dimensions were assessed in 163 Marfan patients (48 % female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. -8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. -18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. -8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. -7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28).
  
  
  CONCLUSIONS
  Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.
authors.affiliation: Department of Cardiology, Academic Medical Center Amsterdam, Rm. F3-147, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Institute of the Netherlands, Interuniversity Cardiology, Utrecht, The Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: den Hartog
authors.affiliation: Department of Cardiology, Academic Medical Center Amsterdam, Rm. F3-147, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Institute of the Netherlands, Interuniversity Cardiology, Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Franken
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: van den Berg
authors.affiliation: Institute of the Netherlands, Interuniversity Cardiology, Utrecht, The Netherlands.|Department of Clinical Epidemiology and Biostatistics, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Cardiology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Timmermans
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Scholte
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: de Waard
authors.affiliation: Department of Radiology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Spijkerboer
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Pals
authors.affiliation: Department of Cardiology, Academic Medical Center Amsterdam, Rm. F3-147, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.|Institute of the Netherlands, Interuniversity Cardiology, Utrecht, The Netherlands.
authors.forename: B J M
authors.initials: BJ
authors.lastname: Mulder
authors.affiliation: Department of Cardiology, Academic Medical Center Amsterdam, Rm. F3-147, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.groenink@amc.uva.nl.|Institute of the Netherlands, Interuniversity Cardiology, Utrecht, The Netherlands. m.groenink@amc.uva.nl.|Department of Radiology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands. m.groenink@amc.uva.nl.
authors.forename: M
authors.initials: M
authors.lastname: Groenink
keywords: Cardiac magnetic resonance imaging; FBN1 mutation classes; Losartan; Marfan syndrome; Ventricular function; Ventricular volumes