EURO PEAN SOCI ETY OF CARDIOLOGY ® Original scientific paper Long-term changes in arterial structure and function and left ventricular geometry after enzyme replacement therapy in patients affected with Fabry disease Ce ´ dric Collin 1,2 , Marie Briet 2 , Thi-Chien Tran 1,2 , He ´le ` ne Beaussier 2 , Karelle Benistan 1 , Mourad Bensalah 3 , Elie Mousseaux 3 , Marc Froissart 4 , Erwan Bozec 2 , Ste ´ phane Laurent 2 , Pierre Boutouyrie 2 and Dominique P Germain 1 Abstract Aims: Fabry disease is a lysosomal storage disorder due to deficient alpha-galactosidase A activity, characterised by glycosphingolipids deposition in tissues. Patients have a common arterial involvement and contract progressive renal and cardiac disease. Although short-term effects of enzyme replacement therapy (ERT) on target organs have been estab- lished, no data are available on the long-term outcome. Methods and results: We studied the effects of ERT (agalsidase beta, 1mg/kg/14 days) on arterial and cardiac structure and function during a longitudinal study beginning in 1999, with 4.5  0.4 years follow-up (four visits) in 30 patients (age: 33  12 years). In addition, we studied 16 untreated Fabry patients during 2.6  1.6 years (two visits). Aortic stiffness was determined by carotid-femoral pulse wave velocity, central pulse pressure by aplanation tonometry, and carotid and radial intima-media thickness and diameter by high definition echotracking device. Left ventricular mass was determined by MRI. A significant decrease in aortic stiffness (0.56  0.13 m/s/yr, p ¼ 0.0002) was observed after ERT whereas central pulse pressure did not change. Carotid intima-media thickness (IMT) increased (þ18  6 mm/yr; p < 0.005) whereas radial IMT remained stable. Radial artery diameter decreased (50  20 mm/years, p < 0.05) whereas carotid diameter did not change. Carotid circumferential wall stress was reduced (1.7  0.6 kPa/yrs, p < 0.01). Left ventricular mass index significantly decreased (7.8  2.3 g/m 2 /yr, p < 0.005). Conclusion: A sustained reduction in aortic stiffness and left ventricular hypertrophy, and a limited radial artery wall thickening were observed after long-term enzyme replacement therapy. There was no significant benefit of treatment on carotid hypertrophy. Keywords Enzyme replacementtherapy, Fabry disease, large- and medium-sized arteries, left ventricular hypertrophy, ultrasonography Received 21 July 2010; accepted 28 October 2010 1 University of Versailles – Saint Quentin en Yvelines (UVSQ), Division of Medical Genetics, Ho ˆpital Raymond Poincare ´ (AP-HP), Garches, France. 2 University Paris Descartes, Assistance Publique – Ho ˆ pitaux de Paris, INSERM U970, Ho ˆpital Europe ´en Georges Pompidou, Department of Pharmacology, Paris, F-75015 France. 3 Assistance Publique – Ho ˆ pitaux de Paris, INSERM U678, Ho ˆ pital Europe ´en Georges Pompidou, Department of Radiology, Paris, F-75015 France. 4 Assistance Publique – Ho ˆ pitaux de Paris, INSERM U1018, Ho ˆ pital Europe ´en Georges Pompidou, Department of Physiology, Paris, F-75015 France. Corresponding author: Dominique P Germain, University of Versailles – Saint Quentin en Yvelines (UVSQ), Division of Medical Genetics, Ho ˆ pital Raymond Poincare ´ (AP-HP), 104 Boulevard Raymond Poincare ´, 92380 Garches, France Email: dominique.germain@rpc.aphp.fr; dominique.germain@uvsq.fr European Journal of Preventive Cardiology 19(1) 43–54 ! The European Society of Cardiology 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1741826710391118 ejpc.sagepub.com Downloaded from https://academic.oup.com/eurjpc/article/19/1/43/5928274 by guest on 09 December 2022