Milani Paolo, Sanna Giuseppe Damiano, Mussinelli Roberta, Basset Marco, Guida Gianluigi, Attanasio Andrea, Nanci Martina, Fabris Francesca, Bellofiore Claudia, Fogliani Alessandro, Novello Elisa, Benigna Francesca, Obici Laura, Benvenuti Pietro, Ciardo Martina, Nuvolone Mario, Averaimo Manuela, Casu Gavino, Foli Andrea, Perlini Stefano, Merlini Giampaolo, Palladini Giovanni
Department of Molecular Medicine University of Pavia Italy.
Amyloidosis Research and Treatment Center Foundation IRCCS Policlinico San Matteo Pavia Italy.
J Am Heart Assoc. 2025 Jan 7;14(1):e036755. doi: 10.1161/JAHA.124.036755. Epub 2024 Dec 24.
For the time being, tafamidis is the only approved treatment for wild-type transthyretin cardiac amyloidosis. However, benefits on all-cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age. We searched baseline variables able to discriminate patients at risk of death within 18 months.
We randomly divided our prospectively maintained database in 2 cohorts, a testing (two thirds) and a validating (one third) set, respectively. We used the Eastern Cooperative Oncology Group-Performance Status as a simple scoring of frailty. We analyzed the clinical, laboratory and instrumental features of 691 consecutive wild-type transthyretin cardiac amyloidosis patients diagnosed between 2006 and 2021. Median follow-up was 43 months, and 367 patients (53%) died. Eighteen-month death was predicted by NT-proBNP (N-terminal pro-B-type natriuretic peptide; cutoff 4200 ng/L), cardiac troponin I (cutoff 92 ng/L), and age (cutoff 80 years). At multivariable analysis, Eastern Cooperative Oncology Group-Performance Status >1 along with the selected variables were independent prognostic determinants and outperformed New York Heart Association functional class. The combination of these variables identified standard- and high-risk patients (all variables above the cutoffs) with a median survival of 57 and 17 months, respectively (<0.001). This was confirmed in the validation set.
A simple scoring system including age, cardiac biomarkers, and Eastern Cooperative Oncology Group-Performance Status identifies subjects with cardiac wild-type transthyretin cardiac amyloidosis at high risk of early death.
目前，塔非酰胺是野生型转甲状腺素蛋白心脏淀粉样变性唯一获批的治疗药物。然而，全因死亡获益仅在约18个月后才显现。当前可用的分期系统无法特异性区分诊断后18个月内死亡风险高的患者，而选择预期从塔非酰胺中获益的患者往往主要（有时甚至仅）基于年龄，由治疗医生进行临床判断。我们寻找能够区分18个月内死亡风险患者的基线变量。
我们将前瞻性维护的数据库随机分为2个队列，分别为测试组（三分之二）和验证组（三分之一）。我们将东部肿瘤协作组体能状态作为虚弱程度的简单评分。我们分析了2006年至2021年间连续诊断的691例野生型转甲状腺素蛋白心脏淀粉样变性患者的临床、实验室和影像学特征。中位随访时间为43个月，367例患者（53%）死亡。N末端B型利钠肽原（NT-proBNP；临界值4200 ng/L）、心肌肌钙蛋白I（临界值92 ng/L）和年龄（临界值80岁）可预测18个月时的死亡情况。在多变量分析中，东部肿瘤协作组体能状态>1以及所选变量是独立的预后决定因素，优于纽约心脏协会心功能分级。这些变量的组合识别出标准风险和高风险患者（所有变量高于临界值），中位生存期分别为57个月和17个月（<0.001）。这在验证组中得到了证实。
一个包括年龄、心脏生物标志物和东部肿瘤协作组体能状态的简单评分系统可识别出野生型转甲状腺素蛋白心脏淀粉样变性早期死亡风险高的患者。
