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Abstract：
BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression.
OBJECTIVE: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA.
METHODS: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677).
RESULTS: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001).
CONCLUSIONS: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA.
OBJECTIVE: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA.
METHODS: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677).
RESULTS: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001).
CONCLUSIONS: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA.
摘要：
背景：转甲状腺素蛋白心脏淀粉样变性（ATTR-CA）是一种进行性心肌病。临床过程因人而异，没有既定的措施来评估疾病进展。
目的：本研究的目的是评估大量ATTR-CA患者中N末端B型利钠肽原（NT-proBNP）升高和门诊利尿剂强化（ODI）作为疾病进展标志物的预后重要性。
方法：我们根据NT-proBNP的恶化和诊断时间与1年访视之间的ODI需求评估了具有里程碑意义的生存分析，来自7个专科中心的2,275例ATTR-CA患者以及随后的死亡率。变量在国家淀粉样变性中心（NAC）队列中开发（n=1,598），并在其余中心的外部队列中验证（n=677）。
结果：在基线和1年访视之间，551（34.5％）NAC患者和204（30.1％）患者在外部验证队列中经历了NT-proBNP进展（NT-proBNP增加>700ng/L和>30％），与死亡率相关(NAC队列:HR:1.82;95%CI:1.57-2.10;P<0.001;验证队列:HR:1.75;95%CI:1.32-2.33;P<0.001)。在1年,451例（28.2%）NAC患者和301例（44.5%）外部验证队列患者经历ODI，与死亡率相关(NAC队列:HR:1.88;95%CI:1.62-2.18;P<0.001;验证队列:HR:2.05;95%CI:1.53-2.74;P<0.001)。与具有稳定的NT-proBNP和稳定的利尿剂剂量的患者相比，在经历NT-proBNP进展或ODI的患者中观察到更高的死亡风险（NAC队列：HR：1.93;95％CI：1.65-2.27;P<0.001;验证队列：HR：1.94;95％CI：1.36-2.77;P<0.001），和那些同时经历NT-proBNP进展和ODI（NAC队列：HR：2.98;95％CI：2.42-3.67;P<0.001;验证队列：HR：3.23;95％CI：2.17-4.79;P<0.001）。
结论：NT-proBNP进展和ODI频繁且与死亡风险增加相关。组合两个变量产生一个简单的，检测ATTR-CA疾病进展的普遍适用模型。
目的：本研究的目的是评估大量ATTR-CA患者中N末端B型利钠肽原（NT-proBNP）升高和门诊利尿剂强化（ODI）作为疾病进展标志物的预后重要性。
方法：我们根据NT-proBNP的恶化和诊断时间与1年访视之间的ODI需求评估了具有里程碑意义的生存分析，来自7个专科中心的2,275例ATTR-CA患者以及随后的死亡率。变量在国家淀粉样变性中心（NAC）队列中开发（n=1,598），并在其余中心的外部队列中验证（n=677）。
结果：在基线和1年访视之间，551（34.5％）NAC患者和204（30.1％）患者在外部验证队列中经历了NT-proBNP进展（NT-proBNP增加>700ng/L和>30％），与死亡率相关(NAC队列:HR:1.82;95%CI:1.57-2.10;P<0.001;验证队列:HR:1.75;95%CI:1.32-2.33;P<0.001)。在1年,451例（28.2%）NAC患者和301例（44.5%）外部验证队列患者经历ODI，与死亡率相关(NAC队列:HR:1.88;95%CI:1.62-2.18;P<0.001;验证队列:HR:2.05;95%CI:1.53-2.74;P<0.001)。与具有稳定的NT-proBNP和稳定的利尿剂剂量的患者相比，在经历NT-proBNP进展或ODI的患者中观察到更高的死亡风险（NAC队列：HR：1.93;95％CI：1.65-2.27;P<0.001;验证队列：HR：1.94;95％CI：1.36-2.77;P<0.001），和那些同时经历NT-proBNP进展和ODI（NAC队列：HR：2.98;95％CI：2.42-3.67;P<0.001;验证队列：HR：3.23;95％CI：2.17-4.79;P<0.001）。
结论：NT-proBNP进展和ODI频繁且与死亡风险增加相关。组合两个变量产生一个简单的，检测ATTR-CA疾病进展的普遍适用模型。
