The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations

Autor: Aeilko H. Zwinderman, V. de Waard, Anje M. Spijkerboer, Janneke Timmermans, M. P. Van Den Berg, M. Groenink, Arthur J.H.A. Scholte, A.W. den Hartog, Gerard Pals, Romy Franken, B.J.M. Mulder
Přispěvatelé: Graduate School, Cardiology, APH - Amsterdam Public Health, Epidemiology and Data Science, ACS - Amsterdam Cardiovascular Sciences, Medical Biochemistry, Other Research, Radiology and Nuclear Medicine, Cardiovascular Centre (CVC), Surgery, RS: FHML non-thematic output, MUMC+: MA Heelkunde (9)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Marfan syndrome
musculoskeletal diseases
medicine.medical_specialty
DIMENSIONS
congenital
hereditary
and neonatal diseases and abnormalities
Ventricular volumes
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
Cardiomyopathy
030204 cardiovascular system & hematology
PRESSURE
Asymptomatic
Losartan
03 medical and health sciences
0302 clinical medicine
Cardiac magnetic resonance imaging
Fibrosis
Internal medicine
Original Article – Point of View
medicine
FIBROSIS
cardiovascular diseases
skin and connective tissue diseases
Ventricular function
CARDIOMYOPATHY
medicine.diagnostic_test
business.industry
ADULTS
medicine.disease
DYSFUNCTION
CLINICAL PHENOTYPES
MICE
030104 developmental biology
Cardiology
cardiovascular system
TRIAL
FBN1 mutation classes
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Haploinsufficiency
medicine.drug
Zdroj: Netherlands heart journal, 24(11), 675-681. Bohn Stafleu van Loghum
Netherlands Heart Journal, 24(11), 675-681
Netherlands Heart Journal, 24(11), 675-681. Bohn, Stafleu, Van Loghum
Netherlands Heart Journal, 24(11), 675-681. Bohn Stafleu van Loghum
Netherlands Heart Journal
Netherlands Heart Journal, 24, 11, pp. 675-681
Netherlands Heart Journal, 24, 675-681
ISSN: 1568-5888
Popis: Contains fulltext : 171721.pdf (Publisher’s version ) (Open Access) 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). CONCLUSION: Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.
Databáze: OpenAIRE
Externí odkaz: