PMID- 29778854 OWN - NLM STAT- MEDLINE DCOM- 20200324 LR - 20200324 IS - 1876-7591 (Electronic) IS - 1876-7591 (Linking) VI - 12 IP - 8 Pt 2 DP - 2019 Aug TI - Proposed Stages of Myocardial Phenotype Development in Fabry Disease. PG - 1673-1683 LID - S1936-878X(18)30307-3 [pii] LID - 10.1016/j.jcmg.2018.03.020 [doi] AB - OBJECTIVES: This study sought to explore the Fabry myocardium in relation to storage, age, sex, structure, function, electrocardiogram changes, blood biomarkers, and inflammation/fibrosis. BACKGROUND: Fabry disease (FD) is a rare, x-linked lysosomal storage disorder. Mortality is mainly cardiovascular with men exhibiting cardiac symptoms earlier than women. By cardiovascular magnetic resonance, native T1 is low in FD because of sphingolipid accumulation. METHODS: A prospective, observational study of 182 FD (167 adults, 15 children; mean age 42 +/- 17 years, 37% male) who underwent cardiovascular magnetic resonance including native T1, late gadolinium enhancement (LGE), and extracellular volume fraction, 12-lead electrocardiogram, and blood biomarkers (troponin and N-terminal pro-brain natriuretic peptide). RESULTS: In children, T1 was never below the normal range, but was lower with age (9 ms/year, r = -0.78 children; r = -0.41 whole cohort; both p < 0.001). Over the whole cohort, the T1 reduction with age was greater and more marked in men (men: -1.9 ms/year, r = -0.51, p < 0.001; women: -1.4 ms/year, r = -0.47 women, p < 0.001). Left ventricular hypertrophy (LVH), LGE, and electrocardiogram abnormalities occur earlier in men. Once LVH occurs, T1 demonstrates major sex dimorphism: with increasing LVH in women, T1 and LVH become uncorrelated (r = -0.239, p = 0.196) but in men, the correlation reverses and T1 increases (toward normal) with LVH (r = 0.631, p < 0.001), a U-shaped relationship of T1 to indexed left ventricular mass in men. CONCLUSIONS: These data suggest that myocyte storage starts in childhood and accumulates faster in men before triggering 2 processes: a sex-independent scar/inflammation regional response (LGE) and, in men, apparent myocyte hypertrophy diluting the T1 lowering of sphingolipid. CI - Copyright (c) 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Nordin, Sabrina AU - Nordin S AD - Cardiology Department, Barts Heart Centre, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. FAU - Kozor, Rebecca AU - Kozor R AD - Sydney Medical School, University of Sydney, Sydney, Australia. FAU - Medina-Menacho, Katia AU - Medina-Menacho K AD - Cardiology Department, Barts Heart Centre, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. FAU - Abdel-Gadir, Amna AU - Abdel-Gadir A AD - Cardiology Department, Barts Heart Centre, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. FAU - Baig, Shanat AU - Baig S AD - Cardiology Department, University Hospitals Birmingham, Birmingham, United Kingdom. FAU - Sado, Daniel M AU - Sado DM AD - King's College London, London, United Kingdom. FAU - Lobascio, Ilaria AU - Lobascio I AD - Cardiology Department, Barts Heart Centre, London, United Kingdom. FAU - Murphy, Elaine AU - Murphy E AD - Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom. FAU - Lachmann, Robin H AU - Lachmann RH AD - Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom. FAU - Mehta, Atul AU - Mehta A AD - Lysosomal Storage Disorder Unit, Royal Free Hospital, London, United Kingdom. FAU - Edwards, Nicola C AU - Edwards NC AD - Cardiology Department, University Hospitals Birmingham, Birmingham, United Kingdom. FAU - Ramaswami, Uma AU - Ramaswami U AD - Lysosomal Storage Disorder Unit, Royal Free Hospital, London, United Kingdom. FAU - Steeds, Richard P AU - Steeds RP AD - Cardiology Department, University Hospitals Birmingham, Birmingham, United Kingdom. FAU - Hughes, Derralynn AU - Hughes D AD - Lysosomal Storage Disorder Unit, Royal Free Hospital, London, United Kingdom. FAU - Moon, James C AU - Moon JC AD - Cardiology Department, Barts Heart Centre, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. Electronic address: j.moon@ucl.ac.uk. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20180516 PL - United States TA - JACC Cardiovasc Imaging JT - JACC. Cardiovascular imaging JID - 101467978 RN - 0 (Contrast Media) RN - 0 (Organometallic Compounds) RN - 0 (Sphingolipids) RN - 6HG8UB2MUY (Meglumine) RN - L0ND3981AG (gadoterate meglumine) RN - Fabry Disease, Cardiac Variant SB - IM CIN - JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 2):1684-1685. PMID: 30553671 MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Arrhythmias, Cardiac/*diagnostic imaging/metabolism/pathology/physiopathology MH - Cardiomyopathies/*diagnostic imaging/metabolism/pathology/physiopathology MH - Child MH - Contrast Media/administration & dosage MH - Disease Progression MH - Fabry Disease/*diagnostic imaging/metabolism/pathology/physiopathology MH - Female MH - Humans MH - Hypertrophy, Left Ventricular/*diagnostic imaging/metabolism/pathology/physiopathology MH - *Magnetic Resonance Imaging MH - Male MH - Meglumine/administration & dosage MH - Middle Aged MH - Myocardium/metabolism/*pathology MH - Organometallic Compounds/administration & dosage MH - Phenotype MH - Predictive Value of Tests MH - Prognosis MH - Prospective Studies MH - Sex Characteristics MH - Sex Factors MH - Sphingolipids/metabolism MH - Ventricular Function, Left MH - Ventricular Remodeling MH - Young Adult OTO - NOTNLM OT - Fabry disease OT - gender OT - native T1 OT - phenotype EDAT- 2018/05/21 06:00 MHDA- 2020/03/25 06:00 CRDT- 2018/05/21 06:00 PHST- 2018/01/04 00:00 [received] PHST- 2018/03/11 00:00 [revised] PHST- 2018/03/30 00:00 [accepted] PHST- 2018/05/21 06:00 [pubmed] PHST- 2020/03/25 06:00 [medline] PHST- 2018/05/21 06:00 [entrez] AID - S1936-878X(18)30307-3 [pii] AID - 10.1016/j.jcmg.2018.03.020 [doi] PST - ppublish SO - JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 2):1673-1683. doi: 10.1016/j.jcmg.2018.03.020. Epub 2018 May 16.