Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom; Institute of Cardiovascular Science, University College London, London, United Kingdom.
Division of Medicine, National Amyloidosis Centre, University College London, London, United Kingdom.
JACC Cardiovasc Imaging. 2021 Jan;14(1):189-199. doi: 10.1016/j.jcmg.2020.07.043. Epub 2020 Oct 28.
The purpose of this study was to determine the effect of patisiran on the cardiac amyloid load as measured by cardiac magnetic resonance and extracellular volume (ECV) mapping in cases of transthyretin cardiomyopathy (ATTR-CM).
Administration of patisiran, a TTR-specific small interfering RNA (siRNA), has been shown to benefit neuropathy in patients with hereditary ATTR amyloidosis, but its effect on ATTR-CM remains uncertain.
Patisiran was administered to 16 patients with hereditary ATTR-CM who underwent assessment protocols at the UK National Amyloidosis Centre. Twelve of those patients concomitantly received diflunisal as a "TTR-stabilizing" drug. Patients underwent serial monitoring using cardiac magnetic resonance, echocardiography, cardiac biomarkers, bone scintigraphy, and 6-min walk tests (6MWTs). Findings of amyloid types and extracellular volumes were compared with those of 16 patients who were retrospectively matched based on cardiac magnetic resonance results.
Patisiran was well tolerated. Median serum TTR knockdown among treated patients was 86% (interquartile range [IQR]: 82% to 90%). A total of 82% of cases showed >80% knockdown. Patisiran therapy was typically associated with a reduction in ECV (adjusted mean difference between groups: -6.2% [95% confidence interval [CI]: -9.5% to -3.0%]; p = 0.001) accompanied by a fall in N-terminal pro-B-type natriuretic peptide concentrations (adjusted mean difference between groups: -1,342 ng/l [95% CI: -2,364 to -322]; p = 0.012); an increase in 6MWT distances (adjusted mean differences between groups: 169 m [95% CI: 57 to 2,80]; p = 0.004) after 12 months of therapy; and a median reduction in cardiac uptake by bone scintigraphy of 19.6% (IQR: 9.8% to 27.1%).
Reductions in ECV by cardiac magnetic resonance provided evidence for ATTR cardiac amyloid regression in a proportion of patients receiving patisiran.
本研究旨在评估 patisiran 对转甲状腺素蛋白心肌病（ATTR-CM）患者心脏淀粉样负荷的影响，采用心脏磁共振和细胞外容积（ECV）图测量。
已有研究表明，针对转甲状腺素蛋白（TTR）的小干扰 RNA（siRNA）patisiran 可改善遗传性 ATTR 淀粉样变性患者的神经病变，但它对 ATTR-CM 的影响尚不确定。
16 例遗传性 ATTR-CM 患者在英国国家淀粉样变性中心接受评估方案，给予 patisiran 治疗。其中 12 例患者同时接受双氯芬酸作为“TTR 稳定剂”。患者接受心脏磁共振、超声心动图、心脏生物标志物、骨闪烁扫描和 6 分钟步行试验（6MWT）的系列监测。比较淀粉样变类型和细胞外容积的发现与根据心脏磁共振结果回顾性匹配的 16 例患者的结果。
patisiran 具有良好的耐受性。治疗患者的血清 TTR 敲低中位数为 86%（四分位距[IQR]：82%90%）。82%的病例显示>80%的敲低。patisiran 治疗通常与 ECV 降低相关（组间调整平均差异：-6.2%[95%置信区间[CI]：-9.5%-3.0%]；p=0.001），并伴有 N 末端 pro-B 型利钠肽浓度下降（组间调整平均差异：-1,342ng/l[95%CI：-2,364-322]；p=0.012）；治疗 12 个月后 6MWT 距离增加（组间调整平均差异：169m[95%CI：572,80]；p=0.004）；骨闪烁扫描显示心脏摄取中位数减少 19.6%（IQR：9.8%~27.1%）。
心脏磁共振测量的 ECV 减少为接受 patisiran 治疗的患者的一部分提供了 ATTR 心脏淀粉样变消退的证据。
