From the Institute of Cardiovascular Science, University College London, United Kingdom (S.N., J.B.A., K.D.K., G.C., T.A.T., J.C.M.).
Cardiology Department, Barts Heart Centre, London, United Kingdom (S.N., J.B.A., K.D.K., G.C., T.A.T., J.C.M.).
Circ Cardiovasc Imaging. 2019 Dec;12(12):e009430. doi: 10.1161/CIRCIMAGING.119.009430. Epub 2019 Dec 12.
Cardiac response to enzyme replacement therapy (ERT) in Fabry disease is typically assessed by measuring left ventricular mass index using echocardiography or cardiovascular magnetic resonance, but neither quantifies myocardial biology. Low native T1 in Fabry disease represents sphingolipid accumulation; late gadolinium enhancement with high T2 and troponin elevation reflects inflammation. We evaluated the effect of ERT on myocardial storage, inflammation, and hypertrophy.
Twenty patients starting ERT (60% left ventricular hypertrophy-positive) were compared with 18 patients with early disease and 18 with advanced disease over 1 year at 3 centers. Cardiovascular magnetic resonance (left ventricular mass index, T1, T2, global longitudinal strain, and late gadolinium enhancement) and biomarkers (high-sensitive troponin-T and NT-proBNP [N-terminal Pro-B-type natriuretic peptide]) at baseline (pre-ERT) and 12 months were performed. Early disease controls were stable, treatment-naïve patients (mainly left ventricular hypertrophy-negative); advanced disease controls were stable, established ERT patients (mainly left ventricular hypertrophy-positive).
Over 1 year, early disease controls increased maximum wall thickness and left ventricular mass index (9.8±2.7 versus 10.2±2.6 mm; =0.010; 65±15 versus 67±16 g/m; =0.005) and native T1 fell (981±58 versus 959±61 ms; =0.002). Advanced disease controls increased T2 in the late gadolinium enhancement area (57±6 versus 60±7 ms; =0.023) with worsening global longitudinal strain (-13.2±3.4 versus -12.1±4.8; =0.039). Newly treated patients had a small reduction in maximum wall thickness (14.8±5.9 versus 14.4±5.7 mm; =0.028), stable left ventricular mass index (93±42 versus 92±40 g/m; =0.186) and a reduction in T1 lowering (917±49 versus 931±54 ms; =0.017).
Fabry myocardial phenotype development is different at different disease stages. After 1 year of ERT initiation, left ventricular hypertrophy-positive patients have a detectable, small reduction in left ventricular mass and storage.
法布瑞病患者接受酶替代疗法（ERT）后的心脏反应通常通过超声心动图或心血管磁共振测量左心室质量指数来评估，但两者都不能定量心肌生物学。法布瑞病中的低 T1 值代表鞘脂堆积；高 T2 值和肌钙蛋白升高的晚期钆增强反映炎症。我们评估了 ERT 对心肌储存、炎症和肥大的影响。
在 3 个中心，20 名开始 ERT（60%左心室肥厚阳性）的患者与 18 名早期患者和 18 名晚期患者进行了比较，随访 1 年。在基线（ERT 前）和 12 个月时进行心血管磁共振（左心室质量指数、T1、T2、整体纵向应变和晚期钆增强）和生物标志物（高敏肌钙蛋白 T 和 NT-proBNP[N-末端 B 型利钠肽前体]）检查。早期疾病对照组为稳定、未接受治疗的患者（主要为左心室肥厚阴性）；晚期疾病对照组为稳定、接受 ERT 治疗的患者（主要为左心室肥厚阳性）。
在 1 年期间，早期疾病对照组的最大壁厚度和左心室质量指数增加（9.8±2.7 与 10.2±2.6mm；=0.010；65±15 与 67±16g/m；=0.005），而 T1 值降低（981±58 与 959±61ms；=0.002）。晚期疾病对照组的晚期钆增强区域的 T2 值增加（57±6 与 60±7ms；=0.023），整体纵向应变恶化（-13.2±3.4 与-12.1±4.8；=0.039）。新接受治疗的患者最大壁厚度略有减少（14.8±5.9 与 14.4±5.7mm；=0.028），左心室质量指数稳定（93±42 与 92±40g/m；=0.186），T1 值降低减少（917±49 与 931±54ms；=0.017）。
法布瑞病心肌表型在不同疾病阶段的发展不同。ERT 治疗开始后 1 年，左心室肥厚阳性患者的左心室质量和储存有可检测到的微小减少。
Zotero 插件
