Abstract：
BACKGROUND: Positron emission tomography/computed tomography (PET/CT) with 18F-florbetapir, a novel amyloid-targeting radiotracer, can quantify left ventricular (LV) amyloid burden in systemic light-chain (AL) amyloidosis. However, its prognostic value is not known.
OBJECTIVE: The authors\' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes.
METHODS: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months.
RESULTS: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage.
CONCLUSIONS: In this first study to link cardiac 18F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE.
OBJECTIVE: The authors\' aim was to evaluate the prognostic value of LV amyloid burden quantified by 18F-florbetapir PET/CT, and to identify mechanistic pathways mediating its association with outcomes.
METHODS: A total of 81 participants with newly diagnosed AL amyloidosis underwent 18F-florbetapir PET/CT imaging. Amyloid burden was quantified using 18F-florbetapir LV uptake as percent injected dose. The Mayo stage for AL amyloidosis was determined using troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain levels. Major adverse cardiac events (MACE) were defined as all-cause death, heart failure hospitalization, or cardiac transplantation within 12 months.
RESULTS: Among participants (median age, 61 years; 57% males), 36% experienced MACE, increasing from 7% to 63% across tertiles of LV amyloid burden (P < 0.001). LV amyloid burden was associated with MACE (HR: 1.46; 95% CI: 1.16-1.83; P = 0.001). However, this association became nonsignificant when adjusted for Mayo stage. In mediation analysis, the association between LV amyloid burden and MACE was mediated by NT-proBNP (P < 0.001), a marker of cardiomyocyte stretch and heart failure, and a component of Mayo stage.
CONCLUSIONS: In this first study to link cardiac 18F-florbetapir uptake to subsequent outcomes, LV amyloid burden estimated by percent injected dose predicted MACE in AL amyloidosis. This effect was not independent of Mayo stage and was mediated primarily through NT-proBNP. These findings provide novel insights into the mechanism linking myocardial amyloid deposits to MACE.
摘要：
背景：使用18F-florbetapir的正电子发射断层扫描/计算机断层扫描（PET/CT），一种新型的淀粉样蛋白靶向放射性示踪剂，可以量化系统性轻链（AL）淀粉样变性中的左心室（LV）淀粉样蛋白负荷。然而,其预后价值尚不清楚。
目的：作者的目的是评估18F-florbetapirPET/CT量化的LV淀粉样蛋白负荷的预后价值，并确定介导其与结果关联的机械途径。
方法：共有81名新诊断为AL淀粉样变性的参与者接受了18F-florbetapirPET/CT显像。淀粉样蛋白负荷使用18F-florbetapirLV摄取作为注射剂量百分比进行定量。使用肌钙蛋白T确定AL淀粉样变的Mayo分期，N末端B型利钠肽原(NT-proBNP),和自由轻链水平。主要不良心脏事件（MACE）定义为全因死亡，心力衰竭住院，或12个月内的心脏移植。
结果：在参与者中(平均年龄，61岁；57%的男性），36%经历过MACE，LV淀粉样蛋白负荷从7%增加到63%(P<0.001)。LV淀粉样蛋白负荷与MACE相关(HR:1.46;95%CI:1.16-1.83;P=0.001)。然而,对Mayo分期进行校正后,这种关联变得不显著.在调解分析中，LV淀粉样蛋白负荷与MACE之间的关联由NT-proBNP介导（P<0.001），心肌细胞拉伸和心力衰竭的标志，也是Mayo舞台的一个组成部分.
结论：在这项将心脏18F-florbetapir摄取与后续结局联系起来的第一项研究中，通过注射剂量百分比估算的LV淀粉样蛋白负荷预测AL淀粉样变性MACE。这种作用并非独立于Mayo阶段,并且主要通过NT-proBNP介导。这些发现为将心肌淀粉样蛋白沉积物与MACE联系起来的机制提供了新的见解。
目的：作者的目的是评估18F-florbetapirPET/CT量化的LV淀粉样蛋白负荷的预后价值，并确定介导其与结果关联的机械途径。
方法：共有81名新诊断为AL淀粉样变性的参与者接受了18F-florbetapirPET/CT显像。淀粉样蛋白负荷使用18F-florbetapirLV摄取作为注射剂量百分比进行定量。使用肌钙蛋白T确定AL淀粉样变的Mayo分期，N末端B型利钠肽原(NT-proBNP),和自由轻链水平。主要不良心脏事件（MACE）定义为全因死亡，心力衰竭住院，或12个月内的心脏移植。
结果：在参与者中(平均年龄，61岁；57%的男性），36%经历过MACE，LV淀粉样蛋白负荷从7%增加到63%(P<0.001)。LV淀粉样蛋白负荷与MACE相关(HR:1.46;95%CI:1.16-1.83;P=0.001)。然而,对Mayo分期进行校正后,这种关联变得不显著.在调解分析中，LV淀粉样蛋白负荷与MACE之间的关联由NT-proBNP介导（P<0.001），心肌细胞拉伸和心力衰竭的标志，也是Mayo舞台的一个组成部分.
结论：在这项将心脏18F-florbetapir摄取与后续结局联系起来的第一项研究中，通过注射剂量百分比估算的LV淀粉样蛋白负荷预测AL淀粉样变性MACE。这种作用并非独立于Mayo阶段,并且主要通过NT-proBNP介导。这些发现为将心肌淀粉样蛋白沉积物与MACE联系起来的机制提供了新的见解。
