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Proposed Stages of Myocardial Phenotype Development in Fabry Disease

Nordin, S; Kozor, R; Medina-Menacho, K; Abdel-Gadir, A; Baig, S; Sado, DM; Lobascio, I; ... Moon, JC; + view all (2018) Proposed Stages of Myocardial Phenotype Development in Fabry Disease. JACC Cardiovasc Imaging 10.1016/j.jcmg.2018.03.020. (In press). Green open access

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Abstract

OBJECTIVES: The authors 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.

Type: Article
Title: Proposed Stages of Myocardial Phenotype Development in Fabry Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jcmg.2018.03.020
Publisher version: https://doi.org/10.1016/j.jcmg.2018.03.020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Fabry disease, gender, native T1, phenotype
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10052329
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