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Proposed Stages of Myocardial Phenotype Development in Fabry Disease

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Sabrina Nordin, Rebecca Kozor, Katia Medina-Menacho, Amna Abdel-Gadir, Shanat Baig, Daniel M. Sado, Ilaria Lobascio, Elaine Murphy, Robin H. Lachmann, Atul Mehta, Nicola C. Edwards, Uma Ramaswami, Richard P. Steeds, Derralynn Hughes, James C. Moon

Original languageEnglish
Number of pages11
JournalJACC Cardiovascular Imaging
Publication statusE-pub ahead of print - 16 May 2018

King's Authors


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.

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