Background Fabry disease (FD) is an X-linked lysosomal storage disorder leading to intracellular accumulation of glycosphingolipid affecting multiple organs including the heart. Cardiac involvement is characterised by progressive left ventricular hypertrophy (LVH), fibrosis and heart failure. Progressive impairment of global longitudinal strain by speckle tracking echocardiography has been extensively described, with its use as a marker of systolic dysfunction validated in patients with advanced FD cardiomyopathy. CMR imaging is now at the forefront in the assessment of cardiovascular complications of FD and is the gold standard for measurement of cardiac volumes, ejection fraction (EF) and mass. Additionally, it allows detection of sphingolipid storage by T1 mapping and functional evaluation using feature tracking. We aim to characterise the relationship between systolic strain and myocardial deposition of sphingolipid across the spectrum of Fabry cardiomyopathy.
Methods This is a cross-sectional, international multicentre study of 166 patients with genetically confirmed FD. All participants underwent CMR (1.5T, Avanto (UK) and Aera (Australia)) using a standardised clinical protocol with late gadolinium enhancement imaging. T1 mapping was performed on basal LV short axis slices using a Modified Look-Locker Inversion recovery (MOLLI) sequence, with region of interest values taken from basal septum. LVH was defined as elevated LV mass indexed for body surface area (LVMi) and low native T1 was defined from normalised reference ranges using healthy volunteers from individual centres (mean±2 SD). Systolic strain parameters (3D peak global longitudinal, GLS; circumferential, GCS; and radial, GRS) were obtained using CVI42 software.
Results The mean age of patients was 44±15.16 years, with 63.9% female (n=106) and 36.1% male (n=60). In those with LVH (LVH+, n=72) low T1 reflecting storage was common (94%), whereas in those without LVH (LVH-, n=94) storage was present in less than half (41.5% low T1 vs 58.5% normal T1). There was no significant correlation between LVEF and LVMi (r=−0.38, p=0.625) but LVMi correlated with impairment of all systolic strain parameters (GLS: r=0.556, p<0.01; GCS: r=0.492, p<0.01; GRS: r=−0.447, p<0.01). In the LVH- population, there were no significant differences in systolic strain (low T1 vs normal T1, GLS: −16.99±2.13 vs −17.14±2.14; GCS: −19.34±2.61 vs −19.13; GRS: 44.25±10.45 vs 42.09±8.12).
Conclusion Increasing LV mass is a marker of progressive FD cardiomyopathy and although not associated with impaired LVEF, is associated with impaired contractility measured by reduced myocardial strain. In early cardiac involvement with sphingolipid storage but no LVH, there is no change in contractility. In summary, impaired myocardial function in FD is a product both of storage and structural change with LVH.
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