Fabry disease (FD) is an X-linked lysosomal storage disease resulting in tissue sphingolipid accumulation. Although storage is important, other processes occur and can be measured including hypertrophy, inflammation and fibrosis. These can be quantified by multi-parametric CMR including cine imaging, T1 and T2 mapping and late gadolinium enhancement (LGE).
Recent developments in CMR perfusion mapping allow rapid in-line perfusion quantification permitting the assessment of microvascular dysfunction. We hypothesized that there is microvascular dysfunction in FD which is associated with storage, fibrosis and oedema.
A prospective, observational study of 44 FD patients (49 years, 43% male, 24 (55%) with left ventricular hypertrophy (LVH)) and 27 healthy controls. Multi-parametric CMR included vasodilator stress perfusion mapping. Myocardial blood flow (MBF) was measured and its associations with other processes investigated.
Compared to LVH- FD, LVH+FD had a higher LV ejection fraction (73% vs 67%, p=0.04), lower T1 (937 vs 985ms, p=0.007), more LGE (85% vs 15%, p<0.001 and a lower stress MBF (1.76 vs 2.36 ml/g/min, p<0.001). The reduction in stress MBF was more pronounce in the subendocardium than subepicardium. LVH-FD had lower stress MBF than controls (2.36 vs 3.00 ml/g/min, p=0.001). Across all FD, LGE and low native T1 were independently associated with reduced stress MBF. On a per-segment basis segment basis, stress MBF was independently associated with increasing wall thickness, decreasing native T1, increasing T2, increasing ECV and LGE.
FD patients have reduced perfusion, particularly in the subendocardium with greater reductions with LVH, storage, oedema and scar. Perfusion is reduced even without LVH suggesting it is an early disease marker.