Department of Cardiology, Queen Elizabeth Hospital, Birmingham, UK.
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Heart. 2019 Mar;105(6):470-476. doi: 10.1136/heartjnl-2018-313699. Epub 2018 Oct 3.
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.
An observational study of 221 FD and 77 healthy volunteers (HVs) who underwent CMR (LV volumes, mass, native T1, GLS, late gadolinium enhancement), ECG and blood biomarkers, as part of the prospective multicentre Fabry400 study.
All FD had normal LV ejection fraction (EF 73%±8%). Mean indexed LV mass (LVMi) was 89±39 g/m in FD and 55.6±10 g/m 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 with those without ECG abnormalities (abnormal: -16.7±3.5 vs normal: -20.2±2.4, p<0.001).
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).
NCT03199001; Results.
在法布里病（FD）中早期检测心脏受累非常重要，因为治疗可能会改变疾病的进程。心血管磁共振（CMR）可以检测到 T1 降低，代表心肌鞘脂储存。在许多疾病中，早期机械功能障碍可能通过异常的整体纵向应变（GLS）来检测。我们探讨了 FD 中早期机械功能障碍和鞘脂沉积之间的关系。
这是一项前瞻性多中心 Fabry400 研究的观察性研究，共纳入 221 例 FD 患者和 77 名健康志愿者（HV），他们接受了 CMR（LV 容积、质量、心肌 T1 值、GLS、晚期钆增强）、心电图和血液生物标志物检查。
所有 FD 患者的左心室射血分数（EF 73%±8%）均正常。FD 患者的平均左心室质量指数（LVMi）为 89±39 g/m，HV 为 55.6±10 g/m。102 例（46%）FD 患者存在左心室肥厚（LVH）。FD 患者的 GLS 与 native T1 呈负相关（r=-0.515，p<0.001）。在无 LVH（早期疾病）的 FD 患者中，随着 native T1 的降低，GLS 受损（r=-0.285，p<0.002）。在 FD 患者中，与心电图正常者相比，心电图异常患者的 GLS 显著受损（异常：-16.7±3.5 vs 正常：-20.2±2.4，p<0.001）。
FD 患者的 GLS 与 LVMi 的增加、储存以及心电图异常有关。在 LVH 阴性 FD（早期疾病）中，GLS 受损与 native T1 的降低有关，提示在出现鞘脂沉积（低 T1）之前就已经出现了机械功能障碍。
NCT03199001；结果。
