Sabrina Nordin1, Rebecca Kozor2, Katia Medina-Menacho1, Amna Abdel-Gadir1, Shanat Baig3, Daniel M Sado4, Ilaria Lobascio5, Elaine Murphy6, Robin H Lachmann6, Atul Mehta7, Nicola C Edwards3, Uma Ramaswami7, Richard P Steeds3, Derralynn Hughes7, James C Moon8. 1. Cardiology Department, Barts Heart Centre, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom. 2. Sydney Medical School, University of Sydney, Sydney, Australia. 3. Cardiology Department, University Hospitals Birmingham, Birmingham, United Kingdom. 4. King's College London, London, United Kingdom. 5. Cardiology Department, Barts Heart Centre, London, United Kingdom. 6. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom. 7. Lysosomal Storage Disorder Unit, Royal Free Hospital, London, United Kingdom. 8. 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.
Abstract
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.
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.
Authors: Kristopher D Knott; Joao B Augusto; Sabrina Nordin; Rebecca Kozor; Claudia Camaioni; Hui Xue; Rebecca K Hughes; Charlotte Manisty; Louise A E Brown; Peter Kellman; Uma Ramaswami; Derralyn Hughes; Sven Plein; James C Moon Journal: Circ Cardiovasc Imaging Date: 2019-07-04 Impact factor: 7.792
Authors: João B Augusto; Nicolas Johner; Dipen Shah; Sabrina Nordin; Kristopher D Knott; Stefania Rosmini; Clement Lau; Mashael Alfarih; Rebecca Hughes; Andreas Seraphim; Ravi Vijapurapu; Anish Bhuva; Linda Lin; Natalia Ojrzyńska; Tarekegn Geberhiwot; Gabriella Captur; Uma Ramaswami; Richard P Steeds; Rebecca Kozor; Derralynn Hughes; James C Moon; Mehdi Namdar Journal: Eur Heart J Cardiovasc Imaging Date: 2021-06-22 Impact factor: 6.875