Author + information
- Received January 4, 2018
- Revision received March 11, 2018
- Accepted March 30, 2018
- Published online August 5, 2019.
- Sabrina Nordin, MBBSa,b,
- Rebecca Kozor, PhDc,
- Katia Medina-Menacho, MDa,b,
- Amna Abdel-Gadir, MBBSa,b,
- Shanat Baig, MBBSd,
- Daniel M. Sado, MDe,
- Ilaria Lobascio, MDa,
- Elaine Murphy, MBBChf,
- Robin H. Lachmann, MD, PhDf,
- Atul Mehta, PhDg,
- Nicola C. Edwards, PhDd,
- Uma Ramaswami, MDg,
- Richard P. Steeds, MDd,
- Derralynn Hughes, PhDg and
- James C. Moon, MDa,b,∗ ()
- aCardiology Department, Barts Heart Centre, London, United Kingdom
- bInstitute of Cardiovascular Science, University College London, London, United Kingdom
- cSydney Medical School, University of Sydney, Sydney, Australia
- dCardiology Department, University Hospitals Birmingham, Birmingham, United Kingdom
- eKing’s College London, London, United Kingdom
- fCharles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom
- gLysosomal Storage Disorder Unit, Royal Free Hospital, London, United Kingdom
- ↵∗Address for correspondence:
Prof. James Moon, Barts Heart Centre, St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, United Kingdom.
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.
This research is supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre. This study is funded by an investigator-led research grant from Genzyme, now Sanofi-Genzyme. Sanofi-Genzyme had no role in the study beyond the initial funding and requiring recruitment milestones as part of financial governance. Dr. Nordin is supported by investigator-led research grant by Sanofi-Genzyme; and has received honoraria from Shire. Dr. Kozor has received honoraria for presenting and advisory board participation as well as support for investigator-led research from Sanofi-Genzyme. Dr. Murphy has received unrestricted educational grants from Sanofi-Genzyme and Shire; and clinical trial funding from Sanofi-Genzyme, Shire, Amicus, and Biomarin. Dr. Lachmann has received honoraria and travel support from Sanofi-Genzyme. Dr. Mehta has received honoraria and grant support for research and educational activities from Shire, Sanofi-Genzyme, and Amicus. Dr. Moon is the principal investigator of the Sanofi-Genzyme research grant that funded this study. All other authors have reported that they have no disclosures relevant to the contents of this paper to disclose.
- Received January 4, 2018.
- Revision received March 11, 2018.
- Accepted March 30, 2018.
- 2019 American College of Cardiology Foundation
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