Ioannou Adam, Cappelli Francesco, Emdin Michele, Nitsche Christian, Longhi Simone, Masri Ahmad, Cipriani Alberto, Zampieri Mattia, Colio Federica, Poledniczek Michael, Porcari Aldostefano, Razvi Yousuf, Aimo Alberto, Vergaro Giuseppe, De Michieli Laura, Rauf Muhammad U, Patel Rishi K, Villanueva Eugenia, Lustig Yael, Venneri Lucia, Martinez-Naharro Ana, Lachmann Helen, Wechalekar Ashutosh, Whelan Carol, Petrie Aviva, Hawkins Philip N, Solomon Scott, Gillmore Julian D, Fontana Marianna
National Amyloidosis Centre, University College London, London, United Kingdom.
Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy.
J Am Coll Cardiol. 2024 Mar 1;83(14):1276-91. doi: 10.1016/j.jacc.2023.12.036.
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.
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.
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).
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).
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.
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。个体的临床病程各不相同，目前尚无评估疾病进展的既定方法。
本研究的目的是评估N末端B型利钠肽原（NT-proBNP）升高和门诊利尿剂强化（ODI）作为ATTR-CA患者大队列中疾病进展标志物的预后重要性。
我们基于NT-proBNP恶化情况以及诊断时间至1年随访期间的ODI需求，对来自7个专科中心的2275例ATTR-CA患者进行了标志性生存分析，并分析了随后的死亡率。这些变量在国家淀粉样变性中心（NAC）队列（n = 1598）中得出，并在其余中心的外部队列（n = 677）中进行了验证。
在基线至1年随访期间，NAC队列中有551例（34.5%）患者，外部验证队列中有204例（30.1%）患者出现NT-proBNP进展（NT-proBNP升高>700 ng/L且>30%），这与死亡率相关（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）。1年时，NAC队列中有451例（28.2%）患者，外部验证队列中有301例（44.5%）患者接受了ODI，这也与死亡率相关（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NT-proBNP和利尿剂剂量稳定的患者相比，出现NT-proBNP进展或ODI的患者死亡风险更高（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），同时出现NT-proBNP进展和ODI的患者死亡风险更高（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）。
NT-proBNP进展和ODI常见且始终与死亡风险增加相关。将这两个变量结合可产生一个简单、普遍适用的模型，用于检测ATTR-CA中的疾病进展。
