Global longitudinal strain, myocardial storage and hypertrophy in Fabry disease

Introduction: Detecting early cardiac involvement in Fabry disease (FD) is important because therapy may alter disease progression. Cardiovascular magnetic resonance (CMR) can detect T1 lowering, representing myocardial sphingolipid storage. In many diseases, early mechanical dysfunction may be detected by abnormal global longitudinal strain (GLS). We explored the relationship of early mechanical dysfunction and sphingolipid deposition in FD.

Methods: An observational study of 221 FD and 77 healthy volunteers (HV) who underwent CMR (LV volumes, mass, native T1, GLS, late gadolinium enhancement), ECG, and blood biomarkers, as part of the prospective multicenter Fabry400 study.

Results: All FD had normal LV ejection fraction (EF 738%). Mean indexed LV mass (LVMi) was 89±39g/m2 in FD and 55.6±10g/m2 in HV. 102 (46%) FD participants had left ventricular hypertrophy (LVH). There was a negative correlation between GLS and native T1 in FD patients (r=-0.515, p<0.001). In FD patients without LVH (early disease), as native T1 reduced there was impairment in GLS (r=-0.285, p<0.002). In the total FD cohort ECG abnormalities were associated with a significant impairment in GLS compared to those without ECG abnormalities (abnormal: -16.7±3.5 vs. normal: -20.2±2.4, p<0.001).

Conclusions: GLS in FD correlates with an increase in LVMi, storage, and the presence of ECG abnormalities. In LVH-negative FD (early disease), impairment in GLS is associated with a reduction in native T1, suggesting that mechanical dysfunction occurs before evidence of sphingolipid deposition (low T1).